399
Views
53
CrossRef citations to date
0
Altmetric
Research Article

Measurement of Cytokines in Clinical Samples Using Immunoassays: Problems and Pitfalls

Pages 131-182 | Published online: 29 Sep 2008

References

  • Gately MK, Wilson DE, Wong HL. Synergy between recombinant interleukin 2 (rIL 2) and IL 2-depleted lymphokine-containing supernatants in facilitating allogeneic human cytolytic T lymphocyte responses in vitro. J Immunol 1986; 136: 1274–82.
  • Kobayashi M, Fitz L, Ryan M, et al. Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes. J Exp Med 1989; 170: 827–45.
  • Wong HL, Wilson DE, Jenson JC, et al. Characterization of a factor(s) which synergizes with recombinant interleukin 2 in promoting allogeneic human cytolytic T-lymphocyte responses in vitro. Cell Immunol 1988; 111: 39–54.
  • Stern AS, Podlaski FJ, Hulmes JD, et al. Purification to homogeneity and partial characterization of cytotoxic lymphocyte maturation factor from human B-lymphoblastoid cells. Proc Natl Acad Sci USA 1990; 87: 6808–12.
  • Jacobs K, Shoemaker C, Rudersdorf R, et al. Isolation and characterization of genomic and cDNA clones of human erythropoietin. Nature 1985; 313: 806–10.
  • Jones TH. Interleukin-6 an endocrine cytokine. Clin Endocrinol 1994; 40: 703–13.
  • Callard R, Gearing A. The cytokine factsbook. 1st ed. London: Academic Press, 1994.
  • Thomson A. The cytokine handbook. 3rd ed. London: Academic Press, 1998.
  • Aggarwal BB, Puri RK (eds.). Human cytokines: their role in disease and therapy. 1st ed. Oxford: Blackwell Science, 1995.
  • Mire-Sluis A, Thorpe R. (eds.) Cytokines. London, UK: Academic Press, 1998.
  • Isaacs A, Lindemann J. Virus interference. I. The interferons. Proc Roy Soc London 1957; 147: 258–67.
  • Bloom BR, Bennett B. Mechanism of a reaction in vitro associated with delayed-type hyper-sensitivity. Science 1966; 153: 80–2.
  • David JR. Delayed hypersensitivity in vitro: its mediation by cell-free substances formed by lymphoid cell-antigen interaction. Proc Natl Acad Sci USA 1966; 56: 72–7.
  • Ruddle NH, Waksman BH. Cytotoxicity mediated by soluble antigen and lymphocytes in delayed hypersensitivity. III. Analysis of mechanism. J Exp Med 1968; 128: 1267–79.
  • Kolb WP, Granger GA. Lymphocyte in vitro cytotoxicity: characterization of human lymphotoxin. Proc Natl Acad Sci USA 1968; 61: 1250–5.
  • Williams TW, Granger GA. Lymphocyte in vitro cytotoxicity: lymphotoxins of several mammalian species. Nature 1968; 219: 1076–7.
  • Elborn JS, Delamare F, Bell SC, et al. Can tumor necrosis factor-a (TNF-a) be reliably measured in blood. Pedriatr Pulmonol 1995; 19: 226–30.
  • Bang P, Baxter RC, Blum WF, et al. Valid measurements of total IGF concentrations in biological fluids. Recommendations from the 3rd International Symposium on Insulin-like Growth Factors. Endocrinology 1995; 136: 816–7.
  • Balkwill FR. Cytokines: a practical approach. 2nd ed. Oxford, UK: IRL Press, 1995.
  • Hoefakker S, Boersma WJ Claassen E. Detection of human cytokines in situ using antibody- and probe-based methods. J Immunol Methods 1995; 185: 149–75.
  • Karr LJ, Panoskaltsis-Mortari A, Li J, et al. In situ hybridization for cytokine mRNA with digoxigenin-labeled riboprobes. Sensitivity of detection and double label applications. J Immunol Methods 1995; 182: 93–106.
  • Dallaman MJ, Montgomery RA, Larsen CP, et al. Cytokine gene expression: analysis using Northern blotting, polymerase chain reaction and in situ hybridization. Immunol Rev 1991; 119: 163–79.
  • Farrar JD, Street NE. A synthetic standard DNA construct for use in quantification of murine cytokine mRNA molecules. Mol Immunol 1995; 32: 991–1000.
  • Gilliland G, Perrin S, Blanchard K, et al. Analysis of cytokine mRNA and DNA: detection and quantitation by competitive polymerase chain reaction. Proc Natl Acad Sci USA 1990; 87: 2725–9.
  • Delassus S. Quantification of cytokine transcripts using polymerase chain reaction. Eur Cytokine Netw 1997; 8: 239–44.
  • Hutchings PR, Cambridge G, Tite JP, et al. The detection and enumeration of cytokine-secreting cells in mice and man and the clinical application of these assays. J Immunol Methods 1989; 120: 1–8.
  • Czerkinsky C, Andersson G, Ekre HP, et al. Reverse ELISPOT assay for clonal analysis of cytokine production. I. Enumeration of gamma-interferon-secreting cells. J Immunol Methods 1988; 110: 29–36.
  • Jung T, Schauer U, Heusser C, et al. Detection of intracellular cytokines by flow cytometry. J Immunol Methods 1993; 159: 197–207.
  • Prussin C, Metcalfe DD. Detection of intracytoplasmic cytokine using flow cytometry and directly conjugated anti-cytokine antibodies. J Immunol Methods 1995; 188: 117–28.
  • Prussin C. Cytokine flow cytometry: understanding cytokine biology at the single-cell level. J Clin Immunol 1997; 17: 195–204.
  • Maino VC, Picker LJ. Identification of functional subsets by flow cytometry: intracellular detection of cytokine expression. Cytometry 1998; 34: 207–15.
  • Mire-Sluis AR, Thorpe R. Laboratory protocols for the quantitation of cytokines by bioassay using cytokine responsive cell lines. J Immunol Methods 1998; 211: 199–210.
  • Kriegler M, Perez C, DeFay K, et al. A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: ramifications for the complex physiology of TNF. Cell 1988; 53: 4553.
  • Kurt-Jones EA, Kiely JM Unanue ER. Conditions required for expression of membrane IL-1 on B cells. J Immunol 1985; 135: 1548–50.
  • Brody DT, Durum SK. Membrane IL-1: IL-1 alpha precursor binds to the plasma membrane via a lectin-like interaction. J Immunol 1989; 143: 1183–7.
  • Mire-Sluis AR, Page L Thorpe R. Quantitative cell line based bioassays for human cytokines. J Immunol Methods 1995; 187: 191–9.
  • Feldkamp, C.S. Smith, SW. In:Practicalguide to immunoassay method evaluation. Chan, D W, Perlstein, MT, eds. Immunoassay: a practical guide. 49–95. San Diego, USA, Academic Press, 1987.
  • Weber TH, Kapyaho KI, Tanner P. Endogenous interference in immunoassays in clinical chemistry: a review. Scand J Clin Lab Invest 1990; 50, Suppl. 201: 82.
  • Pesce AJ, Michael JG. Artifacts and limitations of enzyme immunoassay. J Immunol Methods 1992; 150: 111–9.
  • Roux-Lombard P, Steiner G. Preliminary report on cytokine determination in human synovial fluids: a consensus study of the European Workshop for Rheumatology Research. Clin Exp Rheum 1992; 10: 515–20.
  • Bienvenu J, Coulon L, Doche C, et al. Analytical performances of commercial ELISA-kits for IL-2, IL-6 and TNF-a. A WHO study. Eur Cytokine Netw 1993; 4: 447–51.
  • Ledur A, Fitting C, David B, et al. Variable estimates of cytokine levels produced by commercial ELISA kits: results using international cytokine standards. J Immunol Methods 1995; 186: 171–9.
  • Mire-Sluis AR, Gaines-Das R Padilla A. WHO cytokine standardization: facilitating the development of cytokines in research, diagnosis and as therapeutic agents. J Immunol Methods 1998; 216: 103–16.
  • Mire-Sluis AR, Gaines-Das R, Thorpe R, et al. Implications for the assay and biological activity of interleukin-8: results of a WHO international collaborative study. J Immunol Methods 1997; 200: 1–16.
  • Mire-Sluis AR, Das RG, Thorpe R, et al. Implications for the assay and biological activity of interleukin-4. Results of a WHO international collaborative study. J Immunol Methods 1996; 194: 13–25.
  • Thorpe R. Developments in immunological standardization. J Immunol Methods 1998; 216: 93–101.
  • Wadhwa M, Thorpe R. Standardization and calibration of cytokine immunoassays: meeting report and recommendations. Cytokine 1997; 9: 791–3.
  • De Kossodo S, Houba V, Grau GE, et al. Assaying tumor necrosis factor concentrations in human serum. A WHO International Collaborative Study. J Immunol Methods 1995; 182: 107–14.
  • Kuroki M, Haruno M, Arakawa F, et al. Reaction profiles of seven enzyme immunoassay kits for carcinoembryonic antigen (CEA) analyzed with purified preparations of CEA and related normal antigens. Clin Biochem 1992; 25: 29–35.
  • Pilo A, Zuchelli GC, Chiesa MR, et al. Anomalous between-laboratory variability in a collaborative study of carcinoembryonic antigen immunoassay [letter]. Clin Chem 1987; 33: 1694–5.
  • Nagasaki H, Watanabe S, Kuroki M, et al. An enzyme immunoassay for carcinoembryonic antigen (CEA) with homogeneous reactivity to different CEA preparations and low cross-reactivity with CEA-related normal antigens. J Immunol Methods 1993; 162: 23545.
  • Van den Steen P, Rudd PM, Dwek RA et al. Cytokine and protease glycosylation as a regulatory mechanism in inflammation and autoimmunity. Glycoimmunology 1998; 2: 13343.
  • Taupin J-L, Gualde N Moreau J-F. A monoclonal antibody based ELISA for quantitation of human leukaemia inhibitory factor. Cytokine 1997; 9: 112–8.
  • Bird C, Wadhwa M Thorpe R. Development of immunoassays for human interleukin 3 and interleukin 4, some of which discriminate between different recombinant DNA-derived molecules. Cytokine 1991; 3: 562–7.
  • Smith RA, Baglioni C. The active form of tumor necrosis factor is a trimer. J Biol Chem 1987; 262: 6951–4.
  • Petyovka N, Lyach L Voitenok NN. Homologous ELISA for detection of oligomeric human TNF: properties of the assay. J Immunol Methods 1995; 186: 161–70.
  • Corti A, Fassina G, Marcucci F, et al. Oligomeric tumour necrosis factor alpha slowly converts into inactive forms at bioactive levels. Biochem J 1992; 284: 905–10.
  • De Groote D, Grau GE, Dehart I, et al. Stabilization of functional tumor necrosis factor-a by its soluble TNF receptors. Eur Cytokine Netw 1993; 4: 359–62.
  • Bailly S, Fay M, Ferrua B, et al. Comparative production of IL-1 beta and IL-1 alpha by LPS-stimulated human monocytes: ELISAs measurement revisited. Cytokine 1994; 6: 111–5.
  • Herzyk DJ, Berger AE, Allen JN, et al. Sandwich ELISA formats designed to detect 17 kDa IL-1 beta significantly underestimate 35 kDa IL-1 beta. J Immunol Methods 1992; 148: 24354.
  • Dinarello CA, Clowes GH, Gordon AH, et al. Cleavage of human interleukin 1: isolation of a peptide fragment from plasma of febrile humans and activated monocytes. J Immunol 1984; 133: 1332–8.
  • Laouar A, Villiers C, Sanceau J, et al. Inactivation of interleukin-6 in vitro by monoblastic U937 cell plasma membranes involves both protease and peptidyl-transferase activities. Eur J Biochem 1993; 215: 825–31.
  • Van Kessel KP, Van Strijp JA Verhoef J. Inactivation of recombinant human tumor necrosis factor-alpha by proteolytic enzymes released from stimulated human neutrophils. J Immunol 1991; 147: 3862–8.
  • Scuderi P, Nez PA, Duerr ML, et al. Cathepsin-G and leukocyte elastase inactivate human tumor necrosis factor and lymphotoxin. Cell Immunol 1991; 135: 299–313.
  • Heaney ML, Golde DW. Soluble cytokine receptors. Blood 1996; 87: 847–57.
  • Seckinger P, Isaaz S Dayer J-M. Purification and biologic characterization of a specific tumor necrosis factor inhibitor. J Biol Chem 1989; 264: 11966–73.
  • Engelmann H, Aderka D, Rubinstein M, et al. A tumor necrosis factor-binding protein purified to homogeneity from human urine protects cells from tumor necrosis factor toxicity. J Biol Chem 1989; 264: 11974–80.
  • Gatanaga T, Hwang C, Kohr W, et al. Purification and characterization of an inhibitor (soluble tumour necrosis factor receptor) for tumour necrosis factor and lymphotoxin obtained from the serum ultrafiltrates of human cancer patients. Proc Natl Acad Sci USA 1990; 87: 8781–4.
  • Novick D, Engelmann H, Wallach D, et al. Purification of soluble cytokine receptors from normal human urine by ligand-affinity and immunoaffinity chromotography. Chromatography 1990; 510: 331–7.
  • Novick D, Engelmann H, Wallach D, et al. Soluble cytokine receptors are present in normal human urine. J Exp Med 1989; 170: 1409–14.
  • Rubin LA, Kurman CC, Fritz ME, et al. Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro. J Immunol 1985; 135: 3172–7.
  • Marcon L, Fritz ME, Kurman CC, et al. Soluble Tac peptide is present in the urine of normal individuals and at elevated levels in patients with adult T cell leukaemia (ATL). Clin Exp Immunol 1988; 73: 29–33.
  • Fanslow WC, Clifford K, VandenBos T, et al. A soluble form of the interleukin 4 receptor in biological fluids. Cytokine 1990; 2: 398–401.
  • Fernandez-Botran R, Vitetta ES. A soluble, high-affinity interleukin-4-binding protein is present in the biological fluids of mice. Proc Natl Acad Sci USA 1990; 87: 4202–6.
  • Engelberts I, Stephens S, Francot GJM, et al. Evidence for different effects of soluble TNF-receptors on various TNF measurements in human biological fluids. Lancet 1991; ii: 515–6.
  • Moreau E, Philippe J, Couvent S, et al. Interference of soluble TNF-a receptors in immunological detection of tumor necrosis factor-a. Clin Chem 1996; 42: 1450–3.
  • De Benedetti F, Massa M, Pignatti P, et al. Serum soluble interleukin 6 (IL-6) receptor and IL-6/soluble IL-6 receptor complex in systemic juvenile rheumatoid arthritis. J Clin Invest 1994; 93: 2114–9.
  • Banks RE, Forbes M, Searles J, et al. Evidence for the existence of a novel pregnancy-associated soluble variant of the vascular endothelial growth factor (VEGF) receptor Flt-1. Mol Human Reprod 1998; 4: 377–86.
  • Pitard V, Lorgeot V, Taupin J-L, et al. The presence in human serum of a circulating soluble leukemia inhibitory factor receptor (sgp190) and its evolution during pregnancy. EurCytokine Netw 1998; 9: 599–605.
  • Smith CA, Davis T, Wignall JM, et al. T2 open reading frame from the Shope fibroma virus encodes a soluble form of the TNF receptor. Biochem Biophys Res Commun 1991; 176: 33542.
  • May LT, Viguet H, Kenney JS, et al. High levels of “complexed” interleukin-6 in human blood. J Biol Chem 1992; 267: 19698–704.
  • May LT, Patel K, Garda D, et al. Sustained high levels of circulating chaperoned interleukin-6 after active specific cancer immunotherapy. Blood 1994; 84: 1887–95.
  • May LT, Santhanam U Sehgal PB. On the multimeric nature of natural human interleukin-6. J Biol Chem 1994; 266: 9950–5.
  • May LT, Ndubuisi MI, Patel K, et al. Interleukin-6 chaperones in blood. Ann NY Acad Sci 1995; 762: 120–8.
  • Hansen MB, Svenson M, Diamant M, et al. Anti-interleukin-6 antibodies in normal human serum. Scand J Immunol 1991; 33: 777–81.
  • Hansen MB, Svenson M, Diamant M, et al. High-affinity IgG autoantibodies to IL-6 in sera of normal individuals are competitive inhibitors of IL-6 in vitro. Cytokine 1993; 5: 72–80.
  • Caruso A, Bonfanti C, Colombrita D, et al. Natural antibodies to IFN-gamma in man and their increase during viral infection. J Immunol 1990; 144: 685–90.
  • Panem S, Check IJ, Henriksen D, et al. Antibodies to alpha-interferon in a patient with systemic lupus erythematosus. J Immunol 1982; 129: 1–3.
  • Trown PW, Kramer MJ, Dennin RA, et al. Antibodies to human leucocyte interferons in cancer patients. Lancet 1999; 8316: 81–4.
  • Ross C, Hansen MB, Schyberg T, et al. Autoantibodies to crude human leucocyte interferon (IFN), native human IFN, recombinant human IFN-alpha 2b and human IFN-gamma in healthy blood donors. Clin Exp Immunol 1990; 82: 57–62.
  • Monti E, Pozzi A, Tiberio L, et al. Purification of interleukin-2 antibodies from healthy individuals. Immunol Lett 1993; 36: 261–6.
  • Tiberio L, Caruso A, Pozzi A, et al. The detection and biological activity of human antibodies to IL-2 in normal donors. Scand J Immunol 1993; 38: 472–6.
  • Jeffes IEWB, Ininns EK, Schmitz KL, et al. The presence of antibodies to lymphotoxin and tumor necrosis factor in normal serum. Arth Rheum 1989; 32: 1148–52.
  • Suzuki H, Ayabe T, Kamimura J, et al. Anti-IL-1 autoantibodies in patients with rheumatic diseases and in healthy subjects. Clin Exp Immunol 1991; 85: 407–12.
  • Hansen MB, Svenson M, Abell K, et al. Sex- and age-dependency of IgG auto-antibodies against IL-1 in healthy humans. Eur J Clin Invest 1994; 24: 212–8.
  • Bell JBG, Barfoot R, Iveson T, et al. Neutralizing antibodies in patients with multiple myeloma receiving maintenance therapy with interferon 2b. Br J Cancer 1994; 70: 646–51.
  • Steis RG, Smith JW, Urba WJ, et al. Resistance to recombinant interferon alfa-2a in hairy-cell leukemia associated with neutralizing anti-interferon antibodies. N Engl J Med 1988; 318: 1409–13.
  • Dummer R, Muller W, Nestle F, et al. Formation of neutralizing antibodies against natural interferon-beta, but not against recombinant interferon-gamma during adjuvant therapy for high-risk malignant melanoma patients. Cancer 1991; 67: 2300–4.
  • Scharenberg JGM, Stam AGM, Von Blomberg BME, et al. The development of anti-interleukin-2 (IL-2) antibodies in cancer patients treated with recombinant IL-2. Eur J Cancer 1994; 30A: 1804–9.
  • Allegretta M, Atkins MB, Dempsey RA, et al. The development of anti-interleukin-2 antibodies in patients treated with recombinant human interleukin-2 (IL-2). J Clin Immunol 1986; 6: 481–90.
  • Kirchner H, Korfer A, Evers P, et al. The development of neutralizing antibodies in a patient receiving subcutaneous recombinant and natural interleukin-2. Cancer 1991; 67: 1862–4.
  • Mellstedt H. Induction of anti-granulocyte-macrophage colony-stimulating factor antibodies against exogenous nonglycosylated GM-CSF: biological implications. J Interferon Res 1994; 14: 179–80.
  • Clarke D, Katoh O, Gibbs RV, et al. Interaction of interleukin 7 (IL-7) with glycosaminogly-cans and its biological relevance. Cytokine 1995; 7: 325–30.
  • Gordon MY, Dowding CR, Riley GP, et al. Altered adhesive interactions with marrow stroma of hematopoietic progenitor cells in chronic myeloid leukaemia. Nature 1987; 328: 342–4.
  • McCaffrey TA, Falcone DJ Du B. Transforming growth factor-beta 1 is a heparin-binding protein: identification of putative heparin-binding regions and isolation of heparins with varying affinity for TGF-beta 1. J Cell Physiol 1992; 152: 430–40.
  • Gospodarowicz D, Cheng J. Heparin protects basic and acidic FGF from inactivation. J Cell Physiol 1986; 128: 475–84.
  • Ramsden L, Rider CC. Selective and differential binding of interleukin (IL)-1 alpha, IL-1 beta, IL-2 and IL-6 to glycosaminoglycans. Eur J Immunol 1992; 22: 3027–31.
  • Teodorescu M, Chang J-L Skosey JL. Polyclonal B cell activator associated with alpha-2-macroglobulin in the serum of patients with rheumatoid arthritis. Int Arch Allergy Appl Immunol 1981; 66: 1–12.
  • Borth W, Teoorescu M. Inactivation of human interleukin-2 (IL-2) by a2-macroglobulin-trypsin complexes. Immunology 1986; 57: 367–71.
  • Wollenberg GK, Lamarre J, Rosendal S, et al. Binding of tumor necrosis factor alpha to activated forms of human plasma alpha 2 macroglobulin. Am J Pathol 1991; 138: 265–72.
  • Borth W, Luger TA. Identification of o^-macroglobulin as a cytokine binding plasma protein. J Biol Chem 1989; 264: 5818–25.
  • Borth W, Urbanski A, Prohaska R, et al. Binding of recombinant interleukin-1 P to the third complement component and a2-macroglobulin after activation of serum by immune complexes. Blood 1990; 75: 2388–95.
  • Matsuda T, Hirano T, Nagasawa S, et al. Identification of alpha-2-macroglobulin as a carrier protein for IL-6. J Immunol 1989; 142: 148–52.
  • Ronne H, Anundi H, Rask L, et al. Nerve growth factor binds to serum alpha-2-macroglobulin. Biochem Biophys Res Commun 1979; 87: 330–6.
  • Dennis PA, Saksela O, Harpel P, et al. Alpha 2-macroglobulin is a binding protein for basic fibroblast growth factor. J Biol Chem 1989; 264: 7210–6.
  • Huang SS, O'Grady P Huang JS. Human transforming growth factor p.a2-macroglobulin complex is a latent form of transforming growth factor p. J Biol Chem 1988; 263: 1535–41.
  • Webb DJ, Crookston KP, Hall SW, et al. Binding of transforming growth factor-beta 1 to immobilized human alpha 2-macroglobulin. Arch Biochem Biophys 1992; 292: 487–92.
  • Philip A, O'Connor-McCourt MD. Interaction of transforming growth factor-beta 1 with alpha 2-macroglobulin. Role in transforming growth factor-beta 1 clearance. J Biol Chem 1991; 266: 22290–6.
  • Crookston KP, Webb DJ, Lamarre J, et al. Binding of platelet-derived growth factor-BB and transforming growth factor-P1 to a2-macroglobulin in vitro and in vivo: comparison of receptor-recognized and non-recognized a2-macroglobulin conformations. Biochem J 1993; 293: 443–50.
  • Legres LG, Pochon F, Barray M, et al. Human a2-macroglobulin as a cytokine-binding plasma protein: a study with rh-interleukin-1 P and rh-interleukin-6. Ann NY Acad Sci 1994; 737: 43943.
  • James K, Milne I, Cunningham A, et al. The effect of a2 macroglobulin in commercial cytokine assays. J Immunol Methods 1994; 168: 33–7.
  • Atamas SP. Alternative splice variants of cytokines: making a list. Life Sci 1997; 61: 110512.
  • Onu A, Pohl T, Krause H, et al. Regulation of IL-15 secretion via the leader peptide of two IL-15 isoforms. J Immunol 1997; 158: 255–62.
  • Ladner MB, Martin GA, Noble JA, et al. Human CSF-1: gene structure and alternative splicing of mRNA precursors. EMBO J 1987; 6: 2693–8.
  • Ohtsuki T, Ikeda M, Hatake K, et al. Quantitative analysis of the two macrophage colony-stimulating factor mRNA expressed in a human stromal cell line by reverse transcription-polymerase chain reaction (RT-PCR). Biochim Biophys Acta 1994; 1222: 141–6.
  • Bacic M, Edwards NA Merrill MJ. Differential expression of vascular endothelial growth factor (vascular permeability factor) forms in rat tissues. Growth Factors 1995; 12: 11–5.
  • Tischer E, Mitchell R, Hartman T, et al. The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem 1991; 266: 11947–54.
  • Hauser S, Weich HA. A heparin-binding form of placenta growth factor (PlGF-2) is expressed in human umbilical vein endothelial cells and in placenta. Growth Factors 1993; 9: 259–68.
  • Khachigian LM, Owensby DA Chesterman CN. A tyrosinated peptide representing the alternatively spliced exon of the platelet-derived growth factor A-chain binds specifically to cultured cells and interferes with binding of several growth factors. J Biol Chem 1992; 267: 1660–6.
  • Olofsson B, Pajusola K, Von Euler G, et al. Genomic organization of the mouse and human genes for vascular endothelial growth factor B (VEGF-B) and characterization of a second splice isoform. J Biol Chem 1996; 271: 19310–7.
  • Atamas SP, Choi J, Yurovsky VV, et al. An alternative splice variant of human IL-4, IL-4 delta 2, inhibits IL-4-stimulated T cell proliferation. J Immunol 1996; 156: 435–41.
  • Aziz N, Nishanian P Fahey JL. Levels of cytokines and immune activation markers in plasma in human imunodeficiency virus infection: quality control procedures. Clin Diag Lab Immunol 1998; 5: 755–61.
  • Cannon JG, van der Meer JW, Kwiatkowski D, et al. Interleukin-1 beta in human plasma: optimization of blood collection, plasma extraction and radioimmunoassay methods. Lym-phokine Res 1988; 7: 457–67.
  • De Groote D, Fauchet F, Jadoul M, et al. An ELISA for the measurement of human leukemia inhibitory factor in biological fluids and culture supernatants. J Immunol Methods 1994; 167: 253–61.
  • Boscato LM, Stuart MC. Heterophilic antibodies: a problem for all immunoassays. Clin Chem 1988; 34: 27–33.
  • Boscato LM, Stuart MC. Incidence and specificity of interference in two-site immunoassays. Clin Chem 1986; 32: 1491–5.
  • Persselin JE, Stevens RH. Anti-Fab antibodies in humans. J Clin Invest 1985; 76: 723–30.
  • Dale GL, Gaddy P, Pikul FJ. Antibodies against biotinylated proteins are present in normal human serum. J Lab Clin Med 1994; 123: 365–71.
  • Bubb MO, Green F, Conradie JD, et al. Natural antibodies to avidin in human serum. Immunol Lett 1993; 35: 277–80.
  • Thavasu PW, Longhurst S, Joel SP, et al. Measuring cytokine levels in blood. Importance of anticoagulants, processing and storage conditions. J Immunol Methods 1992; 153: 115–24.
  • De Jongh R, Vranken J, Vundelinckx G, et al. The effects of anticoagulation and processing on assays of IL-6, sIL-6R, sIL-2R and soluble transferrin receptor. Cytokine 1997; 9: 696–701.
  • Kondo S, Asano M, Matsuo K, et al. Vascular endothelial growth factor/vascular permeability factor is detectable in the sera of tumor-bearing mice and cancer patients. Biochim Biophys Acta 1994; 1221: 211–4.
  • Banks RE, Forbes MA, Kinsey SE, et al. Release of the angiogenic cytokine vascular endothelial growth factor (VEGF) from platelets: significance for VEGF measurements and cancer biology. Br J Cancer 1998; 77: 956–64.
  • Katoh O, Tauchi H, Kawaishi K, et al. Expression of the vascular endothelial growth factor (VEGF) receptor gene, KDR, in hematopoietic cells and inhibitory effect of VEGF on apoptotic cell death caused by ionizing radiation. Cancer Res 1995; 55: 5687–92.
  • Wartiovaara U, Salven P, Mikkola H, et al. Peripheral blood platelets express VEGF-C and VEGF that are released during platelet activation. Thromb Hemost 1998; 80: 171–5.
  • Mohle R, Green D, Moore MAS, et al. Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets. Proc Natl Acad Sci USA 1997; 94: 663–8.
  • Freeman MR, Schneck FX, Gagnon ML, et al. Peripheral blood T lymphocytes and lymphocytes infiltrating human cancers express vascular endothelial growth factor: a potential role for T cells in angiogenesis. Cancer Res 1995; 55: 4140–5.
  • Salven P, Orpana A Joensuu H. Leukocytes and platelets of patients with cancer contain high levels of vascular endothelial growth factor. Clin Cancer Res 1999; 5: 487–91.
  • Fava RA, Casey TT, Wilcox J, et al. Synthesis of transforming growth factor-P1 by megakaryocytes and its localization to megakaryocyte and platelet a-granules. Blood 1990; 76: 1946–55.
  • Grainger DJ, Mosedale DE, Metcalfe JC, et al. Active and acid-activatable TGF in human sera, platelets and plasma. Clin Chim Acta 1995; 235: 11–31.
  • Assoian RK, Komoriya A, Meyers CA, et al. Transforming growth factor-P in human platelets. Identification of a major storage site, purification and characterization. J Biol Chem 1983; 258: 7155–60.
  • Merino J, Casado JA, Cid J, et al. The measurement of transforming growth factor type P (TGFP) levels produced by peripheral blood mononuclear cells requires the efficient elimination of contaminating platelets. J Immunol Methods 1992; 153: 151–9.
  • Kropf J, Schurek JO, Wollner A, et al. Immunological measurement of transforming growth factor-beta I (TGF-PI) in blood: assay development and comparison. Clin Chem 1997; 43: 1965–74.
  • Reinhold D, Bank U, Buhling F, et al. A detailed protocol for the measurement of TGF-P1 in human blood samples. J Immunol Methods 1997; 209: 203–6.
  • Grainger DJ, Byrne CD, Witchell CM, et al. Transforming growth factor P is sequested into an inactive pool by lipoproteins. J Lipid Res 1997; 38: 2344–52.
  • Freeman R, Wheeler J, Robertson H, et al. In vitro production of TNF-a in blood samples. Lancet 1990; 336: 312–3.
  • Leroux-Roels G, Offner F, Philippe J, et al. Influence of blood-collecting systems on concentrations of tumor necrosis factor in serum and plasma. Clin Chem 1988; 34: 2373–4.
  • Riches PG, Gooding R. In-vitro production of cytokines in serum. Lancet 1990; 336: 688.
  • Riches P, Gooding R, Millar BC, et al. Influence of collection and separation of blood samples on plasma IL-1, IL-6 and TNF-a concentrations. J Immunol Methods 1992; 153: 125–31.
  • Seiler W, Muller H Hiemke C. Interleukin-6 in plasma collected with an indwelling cannula reflects local, not systemic, concentrations. Clin Chem 1994; 40: 1778–9.
  • Darbonne WC, Rice GC, Mohler MA, et al. Red blood cells are a sink for interleukin 8, a leukocyte chemotaxin. J Clin Invest 1991; 88: 1362–9.
  • Tilg H, Shapiro L, Atkins MB, et al. Induction of circulating and erythrocyte-bound IL-8 by IL-2 immunotherapy and suppression of its in vitro production by IL-1 receptor antagonist and soluble tumor necrosis factor receptor (p75) chimera. J Immunol 1993; 151: 3299–307.
  • Prescott S, James K, Hargreave TB, et al. Radio-immunoassay detection of interferon-gamma in urine after intravesical Evans BCG therapy. J Urol 1990; 144: 1248–51.
  • Bohle A, Nowc C, Ulmer AJ, et al. Elevations of cytokines interleukin-1, interleukin-2 and tumor necrosis factor in the urine of patients after intravesical bacillus Calmette-Guerin immunotherapy. J Urol 1990; 144: 59–64.
  • Martins SM, Darlin DJ, Lad PM, et al. Interleukin-1b: A clinically relevant urinary marker. J Urol 1994; 151: 1198–201.
  • Candela JV, Park E, Gerspach JM, et al. Evaluation of urinary IL-1a and IL-1P in gravid females and patients with bacterial cystitis and microscopic hematuria. Urol Res 1998; 26: 175–80.
  • de Reijke TM, De Boer EC, Kurth KH, et al. Urinary cytokines during intravesical Bacillus Calmette-Guerin therapy for superficial bladder cancer: processing, stability and prognostic value. J Urol 1996; 155: 477–82.
  • Thalmann GN, Dewald B, Baggiolini M, et al. interleukin-8 expression in the urine after bacillus Calmette-Guerin therapy: a potential prognostic factor of tumor recurrence and progression. J Urol 1997; 158: 1340–4.
  • Spong CY, Ghidini A, Ossandon M, et al. Are the cytokines interleukin-6 and angiogenin stable in frozen amniotic fluid. Am J Obst Gynecol 1998; 178: 783–6.
  • Gann PH, Chatterton R, Vogelsong K, et al. Epidermal growth factor-related peptides in human prostatic fluid: sources of variability in assay results. Prostate 1997; 32: 234–40.
  • Gann P, Chatterton R, Vogelsong K, et al. Mitogenic growth factors in breast fluid obtained from healthy women: evaluation of biological and extraneous sources of variability. Cancer Epidem Biomarkers Prev 1997; 6: 421–8.
  • Pahlavani MA, Richardson A. The effect of age on the expression of interleukin-2. Mech Ageing Dev 1996; 89: 125–54.
  • Sindermann J, Kruse A, Frercks H-J, et al. Investigations of the lymphokine system in elderly individuals. Mech Ageing Dev 1993; 70: 149–59.
  • Fagiolo U, Cossarizza A, Scala E, et al. Increased cytokine production in mononuclear cells of healthy elderly people. Eur J Immunol 1993; 23: 2375–8.
  • Straub RH, Konecna L, Hrach S, et al. Serum dehydroepiandrosterone (DHEA) and DHEA sulfate are negatively correlated with serum interleukin-6 (IL-6) and DHEA inhibits IL-6 secretion from mononuclear cells in man in vitro: possible link between endocrinosenescence and immunosenescence. J Clin Endocrinol Metab 1998; 83: 2012–7.
  • Hager K, Machein U, Krieger S, et al. Interleukin-6 and selected plasma proteins in healthy persons of different ages. Neurobiol Aging 1994; 15: 771–2.
  • Wei J, Xu H, Davies JL, et al. Increase of plasma IL-6 concentration with age in healthy subjects. Life Sci 1992; 51: 1953–6.
  • Ershler WB, Sun WH, Binkley N, et al. Interleukin-6 and aging: blood levels and mononuclear cell production increase with advancing age and in vitro production is modifiable by dietary restriction. Lymphokine Cytokine Res 1993; 12: 225–30.
  • Dugue B, Leppanen E. Short-term variability in the concentration of serum interleukin-6 and its soluble receptor in subjectively healthy persons. Clin Chem Lab Med 1998; 36: 323–5.
  • Kania DM, Binkley N, Checovich M, et al. Elevated plasma levels of interleukin-6 in postmenopausal women do not correlate with bone density. J Am Geriatr Soc 1995; 43: 236–9.
  • Lakatos P, Foldes J, Horvath C, et al. Serum interleukin-6 and bone metabolism in patients with thyroid function disorders. J Clin Endocrinol Metab 1997; 82: 78–81.
  • McKane WR, Khosla S, Peterson JM, et al. Circulating levels of cytokines that modulate bone resorption: effects of age and menopause in women. J Bone Miner Res 1994; 9: 1313–8.
  • Jilma B, Dirnberger E, Loscher I, et al. Menstrual cycle-associated changes in blood levels of interleukin-6, a1 acid glycoprotein, and C-reactive protein. J Lab Clin Med 1997; 130: 6975.
  • Janssen JAMJL, Stolk RP, Pols HAP, et al. Serum free IGF-I, total IGF-I, IGFBP1 and IGFBP-3 levels in an elderly population: relation to age and sex steroid levels. Clin Endocrinol 1998; 48: 471–8.
  • Klein NA, Battaglia DE, Miller PB, et al. Circulating levels of growth hormone, insulin-like growth factor-I and growth hormone binding protein in normal women of advanced reproductive age. Clin Endocrinol 1996; 44: 285–92.
  • Landin-Wilhelmsen K, Wilhelmsen L, Lappas G, et al. Serum insulin-like growth factor I in a random population sample of men and women: relation to age, sex, smoking habits, coffee consumption and physical activity, blood pressure and concentrations of plasma lipids, fibrinogen, parathyroid hormone and osteocalcin. Clin Endocrinol 1994; 41: 351–7.
  • Nasu M, Sugimoto T, Chihara M, et al. Effect of natural menopause on serum levels of IGF-I and IGF-binding proteins: relationship with bone mineral density and lipid metabolism in perimenopausal women. Eur J Endocrinol 1997; 136: 608–16.
  • Poehlman ET, Toth MJ, Ades PA, et al. Menopause-associated changes in plasma lipids, insulin-like growth factor I and blood pressure: a longitudinal study. Eur J Clin Invest 1997; 27: 322–6.
  • Sack U, Burkhardt U, Borte M, et al. Age-dependent levels of select immunological mediators in sera of healthy children. Clin DiagLab Immunol 1998; 5: 28–32.
  • Maloney EM, Morris Brown L, Kurman CC, et al. Temporal variability in immunological parameters: peripheral blood mononuclear cell subsets, serum immunoglobulins, and soluble markers of immune system activation. J Clin Lab Anal 1999; 11: 190–5.
  • Diamondstone LS, Tollerud DJ, Fuchs D, et al. Factors influencing serum neopterin and P2-microglobulin levels in a healthy diverse population. J Clin Immunol 1994; 14: 368–74.
  • Tollerud DJ, Brown LM, Blattner WA, et al. Racial differences in serum immunoglobulin levels: relationship to cigarette smoking, T-cell subsets, and soluble interleukin-2 receptors. J Clin Lab Anal 1995; 9: 37–41.
  • Tollerud DJ, Kurman CC, Nelson DL, et al. Racial variation in serum-soluble interleukin-2 receptor levels: a population-based study of healthy smokers and nonsmokers. Clin Immunol Immunopathol 1994; 70: 274–9.
  • Satoh T, Morris Brown L, Blattner WA, et al. Serum neopterin, 2-microglobulin, soluble interleukin-2 receptors, and immunoglobulin levels in healthy adolescents. Clin Immunol Immunopathol 1998; 88: 176–82.
  • Hopkins KD, Lehmann ED, Jones RL, et al. Ethnicity affects IGFBP-3 and IGF-II in normal healthy young adult subjects. Clin Endocrinol 1996; 45: 327–31.
  • Angeli A, Gatti G, Sartori ML, et al. Chronobiological aspects of the neuroendocrine-immune network. Regulation of human natural killer (NK) cell activity as a model. Chronobiology 1992; 19: 93–110.
  • Miyawaki T, Taga K, Nagaoki T, et al. Circadian changes of T lymphocyte subsets in human peripheral blood. Clin Exp Immunol 1984; 55: 618–22.
  • Indiveri F, Pierri I, Rogna S, et al. Circadian variations of autologous mixed lymphocyte reactions and endogenous cortisol. J Immunol Methods 1985; B: 17–24.
  • Kirkham BW, Panayi GS. Diurnal periodicity of cortisol secretion, immune reactivity and disease activity in rheumatoid arthritis: implications for steroid treatment. Br J Rheumatol 1989; 28: 154–7.
  • Barnes PJ. Nuclear factor-kappa B. Int J Biochem Cell Biol 1997; 29: 867–70.
  • Scheinman RI, Cogswell PC, Lofquist AK, et al. Role of transcriptional activation of I kappa B alpha in mediation of immunosuppression by glucocorticoids. Science 1995; 270: 283–6.
  • Barnes PJ. Anti-inflammatory actions of glucocorticoids: molecular mechanisms. Clin Sci 1998; 94: 557–72.
  • Maestroni GJ. The immunoneuroendocrine role of melatonin. J Pineal Res 1993; 14: 1–10.
  • Lissoni P, Barni S, Tancini G, et al. Pineal-opiod system interactions in the control of immunoinflammatory responses. Ann NY Acad Sci 1994; 741: 191–6.
  • Petrovsky N, McNair P Harrison LC. Diurnal rhythms of pro-inflammatory cytokines: regulation by plasma cortisol and therapeutic implications. Cytokine 1998; 10: 307–12.
  • Petrovsky N, Harrison LC. Diurnal rhythmicity of human cytokine production. A dynamic disequilibrium in T helper cell type 1/T helper cell type 2 balance? J Immunol 1997; 158: 5163–8.
  • Born J, Lange T, Hansen K, et al. Effects of sleep and circadian rhythm on human circulating immune cells. J Immunol 1997; 158: 4454–64.
  • Lissoni P, Rovelli F, Brivio O, et al. Circadian secretions of IL-2, IL-12, IL-6 and IL-10 in relation to the light/dark rhythm of the pineal hormone melatonin in healthy humans. Nat Immunity 1998; 16: 1–5.
  • Young MRI, Matthews JP, Kanabrocki EL, et al. Circadian rhythmometry of serum interleukin-2, interleukin-10, tumor necrosis factor-a, and granulocyte-macrophage colony-stimulating factor in men. Chronobiol Int 1995; 12: 19–27.
  • Lemmer B, Schwulera U, Thrun A, et al. Circadian rhythm of soluble interleukin-2 receptor in healthy individuals. Eur Cytokine Netw 1992; 3: 335–6.
  • Gudewill S, Pollmacher T, Vedder H, et al. Nocturnal plasma levels of cytokines in healthy men. Eur Arch Psychiat Clin Neurosci 1992; 242: 53–6.
  • Sothern RB, Roitman-Johnson B, Kanabrocki EL, et al. Circadian characteristics of interleukin-6 in blood and urine of clinically healthy men. In Vivo 1995; 9: 331–9.
  • Takeuchi M, Tanimoto Y, Tada A, et al. Circadian rhythm of plasma levels of endogenous granulocyte colony stimulating factor in healthy volunteers. Int J Hematol 1996; 64: 293–5.
  • Muc-Wierzgon M, Madej K, Baranowski M, et al. Circadian rhythmometry of serum endogenous tumor necrosis factor-alpha in patients with colorectal cancer metastases. Eur Cytokine Netw 1998; 9: 193–6.
  • Crofford LJ, Kalogeras KT, Mastorakos G, et al. Circadian relationship between interleukin (IL)-6 and hypothalamic-pituitary-adrenal axis hormones: failure of IL-6 to cause sustained hypercortisolism in patients with early untreated rheumatoid arthritis. J Clin Endocrinol Metab 1997; 82: 1279–83.
  • Arvidson NG, Gudbjornsson B, Elfman L, et al. Circadian rhythm of serum interleukin-6 in rheumatoid arthritis. Ann Rheum Dis 1994; 53: 521–4.
  • Emile C, Fermand J-P Danon F. Interleukin-6 serum levels in patients with multiple myeloma. Br J Haem 1994; 86: 439–40.
  • Bandieri E, Luppi M, Luppi G, et al. Daily variations of immunoreactive serum interleukin-6 levels in multiple myeloma. Blood 1995; 86: 832–3.
  • Rao KMK, Pieper CS, Currie MS, et al. Variability of plasma IL-6 and crosslinked fibrin dimers over time in community dwelling elderly subjects. Am J Clin Pathol 1994; 102: 8025.
  • Maes M, Stevens W, Scharpe S, et al. Seasonal variation in peripheral blood leukocyte subsets and in serum interleukin-6 and soluble interleukin-2 and -6 receptor concentrations in normal volunteers. Experientia 1994; 50: 821–9.
  • Moynihan JA, Kruszewska B, Brenner GJ, et al. Neural, endocrine and immune system interactions. Relevance for health and disease. Adv Exp Med Biol 1998; 438: 541–9.
  • Marx C, Ehrhart-Bornstein M, Scherbaum WA, et al. Regulation of adrenocortical function by cytokines — relevance for immune-endocrine interaction. Hormone Metabol Res 1998; 30: 416–20.
  • Turnbull AV, Rivier CL. Regulation of the hypothalamic-pituitary-adrenal axis by cytokines: actions and mechanisms of action. Physiol Rev 1999; 79: 1–71.
  • Gaillard RC. Cytokines in the neuroendocrine system. Int Rev Immunol 1998; 17: 181–216.
  • Cannon JG, Dinarello CA. Increased plasma interleukin-1 activity in women after ovulation. Science 1985; 227: 1247–9.
  • Makinoda S, Mikuni M, Sogame M, et al. Erythropoietin, granulocyte-colony stimulating factor, interleukin-1P and interleukin-6 during the normal menstrual cycle. Int J Gynecol Obstet 1996; 55: 265–71.
  • Cannon JG, Abad LW, Vannier E, et al. Menstrual- and gender-dependent variations in circulating IL-1 agonists, antagonists and binding proteins. J Leukocyte Biol 1999; 63: 11723.
  • Angstwurm MWA, Gartner R, Loms Ziegler-Heitbrock HW. Cyclic plasma IL-6 levels during normal menstrual cycle. Cytokine 1997; 9: 370–4.
  • Gorai I, Taguchi Y, Chaki O, et al. Serum soluble interleukin-6 receptor and biochemical markers of bone metabolism show significant variations during the menstrual cycle. J Clin Endocrinol Metab 1998; 83: 326–32.
  • Negami AI, Sasaki H, Kawakami Y, et al. Serum human hepatocyte growth factor in human menstrual cycle and pregnancy: a novel serum marker of regeneration and reconstruction of human endometrium. Hormone Res 1995; 44 Suppl. 2: 42–6.
  • Makinoda S, Mikuni M, Furuta I, et al. Serum concentration of endogenous G-CSF in women during the menstrual cycle and pregnancy. Eur J Clin Invest 1995; 25: 877–9.
  • Maskill JK, Laird SM, Okon M, et al. Stability of serum interleukin-10 levels during the menstrual cycle. Am JReprod Immunol 1997; 38: 339–42.
  • Van Dessel HJHMT, Chandrasekher Y, Yap OWS et al. Serum and follicular fluid levels of insulin-like growth factor I (IGF-I), IGF-II, and IGF-binding protein-1 and-3 during the normal menstrual cycle. J Clin Endocrinol Metab 1996; 81: 1224–31.
  • Wang H-S, Lee J-D Soong Y-K. Serum levels of insulin-like growth factor I and insulin-like growth factor-binding protein-1 and -3 in women with regular menstrual cycles. Fertil Steril 1995; 63: 1204–9.
  • Juul A, Scheike T, Pedersen AT, et al. Changes in serum concentrations of growth hormone, insulin, insulin-like growth factor and insulin-like growth factor-binding proteins 1 and 3 and urinary growth hormone excretion during the menstrual cycle. Hum Reprod 1997; 12: 2123–8.
  • Hyder SM, Stancel GM, Chiappetta C, et al. Uterine expression of vascular endothelial growth factor is increased by estradiol and tamoxifen. Cancer Res 1996; 56: 3954–60.
  • Shifren JL, Tseng JF, Zaloudek CJ, et al. Ovarian steroid regulation of vascular endothelial growth factor in the human endometrium: implications for angiogenesis during the menstrual cycle and in the pathogenesis of endometriosis. J Clin Endocrinol Metab 1996; 81: 3112–8.
  • Greb RR, Heikinheimo O, Williams RF, et al. Vascular endothelial growth factor in primate endometrium is regulated by oestrogen-receptor and progesterone-receptor ligands in vivo. Hum Reprod 1997; 12: 1280–92.
  • Benoy I, Vermeulen P, Wuyts H, et al. Vascular endothelial cell growth factor (VEGF) serum concentrations change according to the phase of the menstrual cycle. Eur J Cancer 1998; 34: 1298–9.
  • Anthony FW, Evans PW, Wheeler T, et al. Variation in detection of VEGF in maternal serum by immunoassay and the possible influence of binding proteins. Ann Clin Biochem 1997; 34: 276–80.
  • Lyall F, Greer IA, Boswell F, et al. Suppression of serum vascular endothelial growth factor immunoreactivity in normal pregnancy and in preeclampsia. Br J Obstet Gynaecol 1997; 104: 223–8.
  • Evans P, Wheeler T, Anthony F, et al. Maternal serum vascular endothelial growth factor during early pregnancy. Clin Sci 1997; 92: 567–71.
  • Evans PW, Wheeler T, Anthony FW, et al. A longitudinal study of maternal serum vascular endothelial growth factor in early pregnancy. Hum Reprod 1998; 13: 1057–62.
  • Sharkey AM, Cooper JC, Balmforth JR, et al. Maternal plasma levels of vascular endothelial growth factor in normotensive pregnancies and in pregnancies complicated by preeclampsia. Eur J Clin Invest 1996; 26: 1182–5.
  • Kupferminc MJ, Daniel Y, Englender T, et al. Vascular endothelial growth factor is increased in patients with preeclampsia. Am J Reprod Immunol 1997; 38: 302–6.
  • Voigt H-J, Steib L. Tumor necrosis factor and pregnancy — a contribution to the immunology of reproduction. Arch Gynecol Obstet 1989; 246: 223–6.
  • Kupferminc MJ, Peaceman AM, Wigton TR, et al. Immunoreactive tumor necrosis factor-alpha is elevated in maternal plasma but undetected in amniotic fluid in the second trimester. Am J Obst Gynecol 1994; 171: 976–9.
  • Conrad KP, Miles TM Fairchild Benyo D. Circulating levels of immunoreactive cytokines in women with preeclampsia. Am J Reprod Immunol 1998; 40: 102–11.
  • Laham N, Brennecke SP, Bendtzen K, et al. Tumour necrosis factor a during human pregnancy and labour: maternal plasma and amniotic fluid concentrations and release from intrauterine tissues. Eur J Endocrinol 1994; 131: 607–14.
  • Vassiliadis S, Ranella A, Papadimitriou L, et al. Serum levels of pro- and anti-inflammatory cytokines in non-pregnant women, during pregnancy, labour and abortion. Mediators Inflamm 1998; 7: 69–72.
  • Opsjon SL, Novick D, Wathen NC, et al. Soluble tumor necrosis factor receptors and soluble interleukin-6 receptor in fetal and maternal sera, coelomic and amniotic fluids in normal and pre-eclamptic pregnancies. J Reprod Immunol 1995; 29: 119–34.
  • Russwurm GP, Mackler AM, Fagoaga OR, et al. Soluble human leukocyte antigens, interleukin-6 and interferon-y during pregnancy. Am J Reprod Immunol 1997; 38: 256–62.
  • Lassarre C, Lalou C, Perin L, et al. Protease-induced alteration of insulin-like growth factor binding protein-3 as detected by radioimmunoassay. Agreement with ligand blotting data. Growth Reg 1994; 4: 48–55.
  • Hossenlopp P, Segovia B, Lassarre C, et al. Evidence of enzymatic degradation of insulin-like growth factor-binding proteins in the 150K complex during pregnancy. J Clin Endocrinol Metab 1990; 71: 797–805.
  • Giudice LC, Farrell EM, Pham H, et al. Insulin-like growth factor binding proteins in maternal serum throughout gestation and in the puerperium: effects of a pregnancy-associated serum protease activity. J Clin Endocrinol Metab 1990; 71: 806–16.
  • Bang P, Fielder PJ. Human pregnancy serum contains at least two distinct proteolytic activities with the ability to degrade insulin-like growth factor binding protein-3. Endocrinology 1999; 138: 3912–7.
  • Kubler B, Cowell S, Zapf J, et al. Proteolysis of insulin-like growth factor binding proteins by a novel 50-kilodalton metalloproteinase in human pregnancy serum. Endocrinology 1998; 139: 1556–63.
  • Claussen M, Zapf J Braulke T. Proteolysis of insulin-like growth factor binding protein-5 by pregnancy serum and amniotic fluid. Endocrinology 1994; 134: 1964–6.
  • Deaciuc IV, Alappat JM, D'Souza NB, et al. Tumor necrosis factor-alpha internalization and degradation by isolated hepatocytes of rats exposed to ethanol. Alcohol 1998; 16: 125–33.
  • Hill DB, Marsano LS McClain CJ. Increased plasma interleukin-8 concentrations in alcoholic hepatitis. Hepatol 1993; 18: 576–80.
  • Sheron N, Bird G, Goka J, et al. Elevated plasma interleukin-6 and increased severity and mortality in alcoholic hepatitis. Clin Exp Immunol 1991; 84: 449–53.
  • Khoruts A, Stahnke L, McClain CJ, et al. Circulating tumor necrosis factor, interleukin-1 and interleukin-6 concentrations in chronic alcoholic patients. Hepatol 1991; 13: 267–76.
  • Bird GL, Sheron N, Goka AK et al. Increased plasma tumor necrosis factor in severe alcoholic hepatitis. Ann Int Med 1990; 112: 917–20.
  • Felver ME, Mezey E, McGuire M, et al. Plasma tumor necrosis factor alpha predicts decreased long-term survival in severe alcoholic hepatitis. Alcohol Clin Exp Res 1990; 14: 255–9.
  • Huang YS, Chan CY, Wu JC, et al. Serum levels of interleukin-8 in alcoholic liver disease: relationship with disease stage, biochemical parameters and survival. J Hepatol 1996; 24: 377–84.
  • Laso FJ, Iglesias MC, Lopez A, et al. Increased interleukin-12 serum levels in chronic alcoholism. J Hepatol 1998; 28: 771–7.
  • Tollerud DJ, Weiss ST Leung DY. Elevated soluble interleukin-2 receptors in young healthy cigarette smokers: lack of association with atopy or airways hyperresponsiveness. Int Arch Allergy Immunol 1992; 97: 25–30.
  • Ginns LC, De Hoyos A, Brown MC, et al. Elevated concentration of soluble interleukin-2 receptors in serum of smokers and patients with lung cancer. Correlation with clinical activity. Am Rev Respir Dis 1990; 142: 398–402.
  • El-Nawawy A, Soliman AT, El-Azzouni O, et al. Effect of passive smoking on frequency of respiratory illnesses and serum immunoglobulin-E (IgE) and interleukin-4 (IL-4) concentrations in exposed children. J Tropical Pedriatr 1996; 42: 166–9.
  • Lesourd BM. Nutrition and immunity in the elderly: modification of immune responses with nutritional treatments. Am J Clin Nutr 1997; 66: 478S-84S.
  • Dandona P, Weinstock R, Thusu K, et al. Tumor necrosis factor-a in sera of obese patients: fall with weight loss. J Clin Endocrinol Metab 1998; 83: 2907–10.
  • Gabriel H, Kindermann W. The acute immune response to exercise: what does it mean? Int J Sports Med 1997; 18: S28–S45.
  • Lackinnon LT. Immunity in athletes. Int J Sports Med 1997; 18: S62–S68.
  • Nieman DC. Exercise immunology: practical applications. Int J Sports Med 1997; 18: S91–S100.
  • Nieman DC. Immune response to heavy exertion. J Appl Physiol 1999; 82: 1385–94.
  • Pedersen BK, Rohde T Ostrowski K. Recovery of the immune system after exercise. Acta Physiol Scand 1998; 162: 325–32.
  • Drenth JPH, Krebbers RJM, Bijzet J, et al. Increased circulating cytokine receptors and ex vivo interleukin-1 receptor antagonist and interleukin-1 production but decreased tumour necrosis factor-a production after a 5-km run. Eur J Clin Invest 1998; 28: 866–72.
  • Smith JA, Telford RD, Baker MS, et al. Cytokine immunoreactivity in plasma does not change after moderate endurance exercise. J Appl Physiol 1992; 73: 1396–401.
  • Nieman DC, Nehlsen-Cannarella SL, Fagoaga OR, et al. Influence of mode and carbohydrate on the cytokine response to heavy exertion. Med Sci Sports Exercise 1997; 30: 671–8.
  • Ullum H, Haahr PM, Diamant M, et al. Bicycle exercise enhances plasma IL-6 but does not change IL-1 a, IL-1P, IL-6, or TNF-a pre-mRNA in BMNC. J Appl Physiol 1994; 77: 93–7.
  • Sprenger H, Jacobs C, Nain M, et al. Enhanced release of cytokines, interleukin-2 receptors, and neopterin after long-distance running. Clin Immunol Immunopathol 1992; 63: 188–95.
  • Drenth JPH, Van Uum SHM, Van Deuren M, et al. Endurance run increases circulating IL-6 and IL-1ra but downregulates ex vivo TNF-a and IL-1 production. J Appl Physiol 1995; 79: 1497–503.
  • Catell LM, Poortmans JR, Leclerq R, et al. Some aspects of the acute phase response after a marathon race, and the effect of glutamine supplementation. Eur J Appl Physiol 1997; 75: 4753.
  • Hornum M, Cooper DM, Brasel JA, et al. Exercise-induced changes in circulating growth factors with cyclic variation in plasma estradiol in women. J Appl Physiol 1997; 82: 1946–51.
  • Vitiello MV, Wilkinson CW, Merriam GR, et al. Successful 6-month endurance training does not alter insulin-like growth factor-I in healthy older men and women. J Gerontol 1997; 52A: M149–M154.
  • Eliakim A, Brasel JA, Mohan S, et al. Increased physical activity and the growth hormone-IGF-I axis in adolescent males. Am J Physiol 1998; 275: R308–R314.
  • Ostrowski K, Rohde T, Zacho M, et al. Evidence that interleukin-6 is produced in human skeletal muscle during prolonged running. J Physiol 1998; 508: 949–53.
  • Bruunsgaard H, Galbo H, Halkjsr-Kristensen J, et al. Exercise-induced increase in serum interleukin-6 in humans is related to muscle damage. J Physiol 1997; 499: 833–41.
  • Sorensen TI, Nielsen GG, Andersen PK, et al. Genetic and environmental influences on premature death in adult adoptees. N Engl J Med 1988; 318: 727–32.
  • Katial RK, Sachanandani D, Pinney C, et al. Cytokine production in cell culture by peripheral blood mononuclear cells from immunocompetent hosts. Clin DiagLab Immunol 1998; 5: 7881.
  • Molvig J, Baek L, Christensen P, et al. Endotoxin-stimulated human monocyte secretion of interleukin 1, tumour necrosis factor alpha, and prostaglandin E2 shows stable interindividual differences. Scand J Immunol 1988; 27: 705–16.
  • Jacob CO, Hwang F, Lewis GD, et al. Tumor necrosis factor alpha in murine systemic lupus erythematosus disease models: implications for genetic predisposition and immune regulation. Cytokine 1991; 3: 551–61.
  • Pociot F, Molvig J, Wogensen L, et al. A tumour necrosis factor beta gene polymorphism in relation to monokine secretion and insulin-dependent diabetes mellitus. Scand J Immunol 1991; 33: 37–49.
  • Molvig J, Pociot F, Baek L, et al. Monocyte function in IDDM patients and healthy individuals. Scand J Immunol 1990; 32: 297–311.
  • Webb GC, Chaplin DD. Genetic variability at the human tumor necrosis factor loci. J Immunol 1990; 145: 1278–85.
  • Messer G, Spengler U, Jung MC, et al. Polymorphic structure of the tumor necrosis factor (TNF) locus: an NcoI polymorphism in the first intron of the human TNF-beta gene correlates with a variant amino acid in position 26 and a reduced level of TNF-beta production. J Exp Med 1991; 173: 209–19.
  • Wilson AG, Di Giovine FS, Blakemore AI, et al. Single base polymorphism in the human tumour necrosis factor alpha (TNF alpha) gene detectable by NcoI restriction of PCR product. Hum Mol Genet 1992; 1: 353.
  • Wilson AG, de Vries N, Pociot F, et al. An allelic polymorphism within the human tumor necrosis factor alpha promoter region is strongly associated with HLA A1, B8, and DR3 alleles. J Exp Med 1993; 177: 557–60.
  • Jacob CO, Fronek Z, Lewis GD, et al. Heritable major histocompatibiity complex class II-associated differences in production of tumour necrosis alpha: Relevance to genetic predisposition to systemic lupus erythematosus. Proc Natl Acad Sci USA 1990; 87: 1233–7.
  • Abraham LJ, French MA Dawkins RL. Polymorphic MHC ancestral haplotypes affect the activity of tumour necrosis factor-alpha. Clin Exp Immunol 1993; 92: 14–8.
  • Brinkman BM, Huizinga TW, Breedveld FC, et al. Allele-specific quantification of TNFA transcripts in rheumatoid arthritis. Hum Genet 1996; 97: 813–8.
  • Louis E, Franchimont D, Piron A, et al. Tumour necrosis factor (TNF) gene polymorphism influences TNF-a production in lipopolysaccharide (LPS)-stimulated whole blood cell culture in healthy humans. Clin Exp Immunol 1998; 113: 401–6.
  • D'Alfonso S, Richiardi PM. A polymorphic variation in a putative regulation box of the TNFA promoter region. Immunogenetics 1994; 39: 150–4.
  • Pociot F, D'Alfonso S, Compasso S, et al. Functional analysis of a new polymorphism in the human TNF a gene promoter. Scand J Immunol 1995; 42: 501–4.
  • Westendorp RGJ, Langermans JAM, Huizinga TWJ, et al. Genetic influence on cytokine production and fatal meningococcal disease. Lancet 1997; 349: 170–3.
  • Booy R, Nadel S, Hibberd M, et al. Genetic influence on cytokine production in meningococcal disease. Lancet 1999; 349: 1176.
  • Nadel S, Newport MJ, Booy R, et al. Variation in the tumor necrosis factor-alpha gene promoter region may be associated with death from meningococcal disease. J Infect Dis 1996; 174: 878–80.
  • Stuber F, Petersen M, Bokelmann F, et al. A genomic polymorphism within the tumor necrosis factor locus influences plasma tumor necrosis factor-alpha concentrations and outcome of patients with severe sepsis. Crit Care Med 1996; 24: 381–4.
  • Bailly S, Di Giovine FS, Blakemore AI, et al. Genetic polymorphism of human interleukin-1 alpha. Eur J Immunol 1993; 23: 1240–5.
  • Di Giovine FS, Takhsh E, Blakemore AI, et al. Single base polymorphism at —511 in the human interleukin-1 beta gene (IL1 beta). Hum Mol Genet 1992; 1: 450.
  • McDowell TL, Symons JA, Ploski R, et al. A genetic association between juvenile rheumatoid arthritis and a novel interleukin-1a polymorphism. Arth Rheum 1995; 38: 221–8.
  • Tarlow JK, Blakemore AI, Lennard A, et al. Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat. Hum Genet 1993; 91: 403–4.
  • Pociot F, Molvig J, Wogensen L, et al. A TaqI polymorphism in the human interleukin-1 beta (IL-1 beta) gene correlates with IL-1 beta secretion in vitro. Eur J Clin Invest 1992; 22: 396402.
  • Turner DM, Williams DM, Sankaran D, et al. An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 1997; 24: 1–8.
  • Eskdale J, Gallagher G. A polymorphic dinucleotide repeat in the human IL-10 promoter. Immunogenetics 1995; 42: 444–5.
  • Fishman D, Faulds G, Jeffery R, et al. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest 1998; 102: 1369–76.
  • Ferraiolo BL, McCabe J, Hollenbach S, et al. Pharmacokinetics of recombinant human tumour necrosis factor-alpha in rats. Effects of size and number of doses and nephrectomy. Drug Metab Disposition 1989; 17: 369–72.
  • Pessina GP, Pacini A, Bocci V, et al. Studies on tumour necrosis factor (TNF): II Metabolic fate and distribution of human recombinant TNF. Lymphokine Res 1987; 6: 35–44.
  • Beutler BA, Milsark IW Cerami A. Cachectin/tumour necrosis factor: production, distribution and metabolic fate in vivo. J Immunol 1985; 135: 3972–7.
  • Bemelmans MH, Gouma DJ Buurman WA. Influence of nephrectomy on tumor necrosis factor clearance in a murine model. J Immunol 1993; 150: 2007–17.
  • Ma Y, Hurst HE Fernandez-Botran R. Soluble cytokine receptors as carrier proteins: effects of soluble interleukin-4 receptors on the pharmacokinetics of murine interleukin-4. J Pharmacol Exp Ther 1996; 279: 340–50.
  • Kudo S, Mizuno K, Hirai Y, et al. Clearance and tissue distribution of recombinant human interleukin-1 beta in rats. Cancer Res 1990; 50: 5751–5.
  • Reimers J, Wogensen LD, Welinder B, et al. The pharmacokinetics, distribution and degradation of human recombinant interleukin 1 beta in normal rats. Scand J Immunol 1991; 34: 597610.
  • Newton RC, Uhl J, Covington M, et al. The distribution and clearance of radiolabelled human interleukin-1 beta in mice. Lymphokine Res 1988; 7: 207–16.
  • Donohue JH, Rosenberg SA. The fate of interleukin-2 after in vivo administration. J Immunol 1983; 130: 2203–8.
  • Ohnishi H, Chao JTY, Lin KKM, et al. Role of the kidney in metabolic change of interleukin-2. Tumor Biol 1989; 10: 202–14.
  • Bocci V, Pacini A, Muscettola M, et al. Renal filtration, absorption and catabolism of human alpha interferon. J Interferon Res 1981; 1: 347–52.
  • Bino T, Edery H, Gertler A, et al. Involvement of the kidney in catabolism of human leukocyte interferon. J Gen Virol 1982; 59: 39–45.
  • Bino T, Madar Z, Gertler A, et al. The kidney is the main site of interferon degradation. J Interferon Res 1982; 2: 301–8.
  • Bocci V, Pacini A, Muscettola M, et al. The kidney is the main site of interferon catabolism. J Interferon Res 1982; 2: 309–14.
  • Bocci V. Renal catabolism of interferons, interleukins 1 and 2 and tumor necrosis factor. Contrib Nephrol 1988; 68: 53–7.
  • Banks RE, Forbes MA, Hallam S, et al. Treatment of metastatic renal cell carcinoma with subcutaneous interleukin 2: evidence for non-renal clearance of cytokines. Br J Cancer 1997; 75: 1842–8.
  • Halwachs G, Tiran A, Reisinger EC, et al. Serum levels of the soluble receptor for tumor necrosis factor in patients with renal disease. Clin Invest 1994; 72: 473–6.
  • Castell JV, Geiger T, Gross V, et al. Plasma clearance, organ distribution and target cells of interleukin-6/hepatocyte-stimulating factor in the rat. Eur J Biochem 1988; 177: 357–61.
  • Sonne O, Davidsen O, Moller BK, et al. Cellular targets and receptors for interleukin-6. I. In vivo and in vitro uptake of IL-6 in liver and hepatocytes. Eur J Clin Invest 1990; 20: 366–76.
  • Cannon JG. Adaptive interactions between cytokines and the hypothalamic-pituitary-gonadal axis. Ann NY Acad Sci 1998; 856: 234–42.
  • Moreira AL, Sampaio EP, Zmuidzinas A, et al. Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation. J Exp Med 1993; 177: 167580.
  • Rogers A, Eastell R. Effects of estrogen therapy of postmenopausal women on cytokines measured in peripheral blood. J Bone Miner Res 1998; 13: 1577–86.
  • Wooley JA, Seleem S, Hills FA, et al. Raised circulating levels of interleukin-6 in women with an intrauterine contraceptive device. Gynecol Obstet Invest 1996; 42: 241–3.
  • Ammala M, Nyman T, Strengell L, et al. Effect of intrauterine contraceptive devices on cytokine messenger ribonucleic acid expression in the human endometrium. Fertil Steril 1995; 63: 773–8.
  • Neveu PJ. Asymmetrical brain modulation of the immune response. Brian Res 1992; 17: 1017.
  • Searleman A, Fugagli AK. Suspected autoimmune disorders and left-handedness: evidence from individuals with diabetes, Crohn's disease and ulcerative colitis. Neuropsychologia 1987; 25: 367–74.
  • Smith J. Left-handedness: its association with allergic diseases. Neuropsychologia 1987; 25: 665–74.
  • Chengappa KNR, Ganguli R, Yang ZW, et al. Differences in serum interleukin-6 (IL-6) between healthy dextral and non-dextral subjects. Neurosci Res 1994; 20: 185–8.
  • Barnes A. Measurment of serum cytokines. Lancet 1998; 352: 324–5.
  • Piscitelli SC, Reiss WG, Figg WD, et al. Pharmacokinetic studies with recombinant cytokines. Scientific issues and practical considerations. Clin Pharmacokinet 1997; 32: 368–81.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.