Endotoxin antagonism: conceptual basis and therapeutic potential

Bibliography

• PFEIFFER R: Untersuchungen ilber das Choleragift. Z Hygiene (1892) 11:393–412.
   Google Scholar
• LUDERITZ 0, GALANOS C, LEHMANN V etal.: Lipid A: chemical structure and biological activity. I Infect. Dis. (1973) 128:29.
   Google Scholar
• SCHROMM AB, BRANDENBURG K, LOPPNOW H et al.: The charge of endotoxin molecules influences their conformation and IL- 6-inducing capacity. Immurial. (1998) 161:5464–5471.
   Google Scholar
• MUNFORD RS, HALL CL: Detoxification of bacterial lipopolysaccharides (endotoxins) by a human neutrophil enzyme. Science (1986) 234:203–205.
   PubMed Web of Science ®Google Scholar
• GOLENBOCK DT, HAMPTON RY, QURESHI N, TAKAYAMA K, RAETZ CR: Lipid A-like molecules that antagonize the effects of endotoxins on human monocytes.J. Biol. Chem. (1991) 266:19490–19498.
   PubMed Web of Science ®Google Scholar
• BAKER PJ, HRABA T, TAYLOR CE etal.:Molecular structures that influence the immunomodulatory properties of the lipid A and inner core region oligosaccharides of bacterial lipopolysaccharides. Infect. Immuri. (1994) 62:2257–2269.
   Google Scholar
• BAKER PJ, HRABA T, TAYLOR CE et al: Structural features that influence the ability of lipid A and its analogs to abolish expression of suppressor T cell activity. Infect. Immuri. (1992) 60:2694–2701.
   PubMed Web of Science ®Google Scholar
• KUMAZAWA Y, MATSUURA M, MARUYAMA T etal.: Structural requirements for inducing in vitro B lymphocyte activation by chemically synthesized derivatives related to the nonreducing D-glucosamine subunit of lipid A. Eur. Immurial. (1986) 16:1099–1103.
   Google Scholar
• HOMMA JY, MATSUURA M, KUMAZAWA Y: Structure-activity relationship of chemically synthesized nonreducing parts of lipid A analogs. Adv. Exp. Med. Biol. (1990) 256:101–119.
   PubMedGoogle Scholar
• MICHALEK SM, MOORE RN, MCGHEE JR, ROSENSTREICH DL, MERGENHAGEN SE: The primary role of lymphoreticular cells in the mediation of host responses to bacterial endotoxin. Dis. (1980) 141:55–63.
   Google Scholar
• •The first conclusive demonstration that the lethal effect of LPS is mediated solely by cells of haematopoietic origin, to the exclusion of other somatic cells.
   Google Scholar
• BERNHEIM HA, BLOCK LH, ATKINS E: Fever: pathogenesis, pathophysiology and purpose. Ann. Intern. Med. (1979) 91:261–270.
   PubMed Web of Science ®Google Scholar
• PENNICA D, NEDWIN GE, HAYFLICK JS et al: Human tumor necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature (1984) 312:724–729.
   PubMed Web of Science ®Google Scholar
• BEUTLER B, MAHONEY J, LE TRANG N, PEKALA P, CERAMI A: Purification of cachectin, a lipoprotein lipase-suppressing hormone secreted by endotoxin-induced RAW 264.7 cells. j Exp. Med. (1985) 161:984–995.
   PubMed Web of Science ®Google Scholar
• BEUTLER B, GREENWALD D, HULMES JD et al: Identity of tumour necrosis factor and the macrophage-secreted factor cachectin. Nature (1985) 316:552–554.
   PubMed Web of Science ®Google Scholar
• MATTHEWS N: Tumour-necrosis factor from the rabbit. V. Synthesis in vitro by mononuclear phagocytes from various tissues of normal and BCG-injected rabbits. Br. J. Cancer (1981) 44:418–424.
   Google Scholar
• HEPPNER G, WEISS DW: High susceptibility of strain A mice to endotoxin and endotoxin-red blood cell mixtures. J. Bacterial (1965) 90:696–703.
   PubMed Web of Science ®Google Scholar
• SULTZER BM: Genetic control of leucocyte responses to endotoxin. Nature (1968) 219:1253–1254.
   PubMed Web of Science ®Google Scholar
• WATSON J, RIBLET R, TAYLOR BA: The response of recombinant inbred strains of mice to bacterial lipopolysaccharides. J. Immune]. (1977) 118:2088–2093.
   PubMed Web of Science ®Google Scholar
• WATSON J, KELLY K, LARGEN M, TAYLOR BA: The genetic mapping of a defective LPS response gene in C3H/FleJ mice. j Immune]. (1978) 120:422–424.
   PubMed Web of Science ®Google Scholar
• POLTORAK A, SMIRNOVA I, HE XL et al.: Genetic and physical mapping of the Lps locus - identification of the toll 4 receptor as a candidate gene in the critical region. Blood Cells Mal Dis. (1998) 24:340–355.
   PubMed Web of Science ®Google Scholar
• ••In this, the earliest publication suggestingthe specific microbe-sensing function fo the TLRs (September 15, 1998), the TLR4 locus is named as the sole candidate gene within the LPS critical region, established by meiotic mapping. In effect, TLR4 is identified as a solitary receptor for LPS, though the mutation that destroys this protein in C3H/HeJ mice is not disclosed.
   Google Scholar
• •• An archival work detailing construction of the contig and the genetic mapping effort that preceded it, this paper laid the groundwork for the Science publication cited as [21], which appeared in print two months later.
   Google Scholar
• POLTORAK A, HEX, SMIRNOVA I et al.: Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in TIr4 gene. Science (1998) 282:2085–2088.
   PubMed Web of Science ®Google Scholar
• ••Following upon the demonstration thatTLR4 was the sole gene within the LPS critical region, the mutations that confer LPS resistance in C3H/HeJ and C57BL/ 10ScCr mice are presented: conclusive proof that TLR4 is the mammalian LPS sensor. Within the text of the paper, doubt is expressed concerning concurrent claims that TLR2-not TLR4-serves this role.
   Google Scholar
• MCCARTHY JV, NI J, DIXIT VM: RIP2 is a novel NF-kappaB-activating and cell death-inducing kinase. j Biol. Chem. (1998) 273:16968–16975.
   PubMed Web of Science ®Google Scholar
• BIHL F, LARIVIERE L, QURESHI ST, FLAHERTY L, MALO D: LPS-hyporesponsiveness of mnd mice is associated with a mutation in Toll-like receptor 4. Genes Immun. (2001) 2:56–59.
   PubMed Web of Science ®Google Scholar
• O'BRIEN AD, ROSENSTREICH DL, SCHER I et al.: Genetic control of susceptibility to Salmonella typhimurium in mice: role of the LPS gene. j Immunol. (1980) 124:20–24.
   Google Scholar
• ROSENSTREICH DL, WEINBLATT AC, O'BRIEN AD: Genetic control of resistance to infection in mice. CRC Crit. Rev Immunol. (1982) 3:263–330.
   Google Scholar
• DING AH, PORTEU E SANCHEZ E, NATHAN CF: Shared actions of endotoxin and taxol on TNF receptors and TNF release. Science (1990) 248:370–372.
   PubMed Web of Science ®Google Scholar
• BELVIN MP, ANDERSON KV: A conserved signaling pathway: the Drosophila toll-dorsal pathway. Ann. Rev Cell Dev. Biol. (1996) 12:393–416.
   PubMed Web of Science ®Google Scholar
• NONAKA M, HUANG ZM: Interleukin-1-mediated enhancement of mouse factor B gene expression via NF kappa B-like hepatoma nuclear factor. Mol. Cell Biol. (1990) 10:6283–6289.
   PubMed Web of Science ®Google Scholar
• MEDZHITOV R, PRESTON-HURLBURT P, JANEWAY CA JR: A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature (1997) 388:394–397.
   PubMed Web of Science ®Google Scholar
• HOSHINO K, TAKEUCHI 0, KAWAI T eta].: Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: Evidence for TLR4 as the Lps gene product. J. Immunol. (1999) 162:3749–3752.
   Google Scholar
• TAKEUCHI 0, HOSHINO K, KAWAI T et al.: Differential roles of TLR2 and TLR4 in recognition of Gram-negative and Gram-positive bacterial cell wall components. Immunity (1999) 11:443–451.
   Google Scholar
• LEMAITRE B, NICOLAS E, MICHAUT L, REICHHART JM, HOFFMANN JA: The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell (1996) 86:973–983.
   PubMed Web of Science ®Google Scholar
• ••Foreshadowing the determination thatTLR4 acts as the mammalian LPS receptor, Toll was identified as a an essential signaling protein in the Drosophila response to fungal infection.
   Google Scholar
• POLTORAK A, RICCIARDI-CASTAGNOLI E CITTERIO A, BEUTLER B: Physical contact between LPS and T1r4 revealed by genetic complementation. Proc. Natl. Acad. Li. USA (2000) 97:2163–2167.
   PubMed Web of Science ®Google Scholar
• ••Using a genetic complementationapproach which entailed the use of immortalized C3H/HeJ macrophages, the species origin of TLR4 was shown to determine ligand preference; hence, LPS may be said to bind TLR4 as a concomitant of signal initiation.
   Google Scholar
• LIEN E, MEANS TK, HEINE H et al.: Toll-like receptor 4 imparts ligand-specific recognition of bacterial lipopolysaccharide. Chu. Invest. (2000) 105:497–504.
   PubMed Web of Science ®Google Scholar
• •Using an approach very similar to that offered in [33], but relying upon CHO cells as their experimental model, Lien and colleagues also conclude that TLR4 must engage LPS in order for signal transduction to occur.
   Google Scholar
• BAUER S, KIRSCHNING CJ, HACKER H et al.: Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Proc. Natl. Acad. Sci. USA (2001) 98:9237–9242.
   PubMed Web of Science ®Google Scholar
• COUTINHO A, MEO T: Genetic basis for unresponsiveness to lipopolysaccharide in C57BL/10Cr mice. Immunogenetics (1978) 7:17–24.
   PubMed Web of Science ®Google Scholar
• ROSENSTREICH DL, VOGEL SN, JACQUES AR, WAHL LM, OPPENHEIM JJ: Macrophage sensitivity to endotoxin. Genetic control by a single codominant gene. j Immunol. (1978) 121:1664–1670.
   Google Scholar
• DU X, POLTORAK A, SILVA M, BEUTLER B: Analysis of TLR4-mediated LPS signal transduction in macrophages by mutational modification of the receptor. Blood Cells Ma Dis. (1999) 25:328–338.
   PubMed Web of Science ®Google Scholar
• •Transfection studies reveal that deletion of the TLR4 cytoplasmic domain does not confer dominant inhibition comparable to that conferred by the point mutation present in the TLR4 protein of C3H/HeJ mice. Moreover, calculation suggests that less than 1000 TLR4 protein molecules are present per LPS responsive macrophage.
   Google Scholar
• NOMURA E AKASHI S, SAKAO Y et al.: Cutting edge: endotoxin tolerance in mouse peritoneal macrophages correlates with down-regulation of surface Toll-like receptor 4 expression. j Immunol. (2000) 164:3476–3479.
   Google Scholar
• FAVORITE GO, MORGAN HR: Effects produced by the intravenous injection in man of a toxic antigenic material derived from Eberthella thyphosa: clinical, hematological, chemical and serological studies. j Chu. Invest. (1942) 21:589–599.
   PubMedGoogle Scholar
• BERRY LJ, SMYTHE DS: Some metabolic aspects of tolerance to bacterial endotoxin. J. Bacteria (1965) 90:970–977.
   PubMed Web of Science ®Google Scholar
• MATHISON JC, VIRCA GD, WOLFSON E et al.: Adaptation to bacterial lipopolysaccharide controls lipopolysaccharide-induced tumor necrosis factor production in rabbit macrophages. Clin. Invest. (1990) 85:1108–1118.
   Google Scholar
• KAWAI T, ADACHI 0, OGAWA T, TAKEDAK, AKIRA S: Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity (1999) 11:115–122.
   PubMed Web of Science ®Google Scholar
• SCHNARE M, HOLTDAGGER AC, TAKEDA K, AKIRA S, MEDZHITOV R: Recognition of CpG DNA is mediated by signaling pathways dependent on the adaptor protein MyD88. Curr. Biol. (2000) 10:1139–1142.
   PubMed Web of Science ®Google Scholar
• TAKEUCHI 0, KAUFMANN A, GROTE K et al.: Preferentially the R-stereoisomer of the mycoplasmal lipopeptide macrophage-activating lipopeptide-2 activates immune cells through a Toll-like receptor 2- and MyD88-dependent signaling pathway. J. Immunol. (2000) 164:554–557.
   Google Scholar
• ADACHI 0, KAWAI T, TAKEDA K et al.: Targeted disruption of the MyD88 gene results in loss of IL-1 and IL-18-mediated function. Immunity (1998) 9:143–150.
   Google Scholar
• FITZGERALD KA, PALSSON-MCDERMOTT EM, BOWIE AG etal.: Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction. Nature (2001) 413:78–83.
   Google Scholar
• HORNG T, BARTON GM, MEDZHITOV R: TIRAP: an adapter molecule in the Toll signaling pathway. Nat. Immurrol. (2001) 2:835–841.
   PubMed Web of Science ®Google Scholar
• JAQUES R, JAQUET H: The duration of action of certain corticosteroids in the acutely adrenalectomized rat as estimated by reference to their protective effect in endotoxin shock. Experientia (1964) 20:230–231.
   PubMedGoogle Scholar
• KRECKE HJ, WILLMANN M, URBASCHEK B, FRITSCH H: On the effect of endotoxin on a biologic membrane (isolated frog skin) and its modification by drugs. Verh. Dtsch. Ces. Inn. Med. (1968) 74:1147–1151.
   PubMedGoogle Scholar
• VERNON-ROBERTS B: The effects of steroid hormones on macrophage activity. Int. Rev Cytol. (1969) 25:131–159.
   PubMedGoogle Scholar
• AGARWAL MK: Assessment of the natureof reticuloendothelial contribution during endotoxicosis in mice. J. Reticuloendothel. Soc. (1972) 12 :40–52.
   PubMedGoogle Scholar
• MOORE RN, GOODRUM KJ, BERRY LJ: Mediation of an endotoxic effect by macrophages. J. Reticuloendothel. Soc. (1976) 19:187–197.
   PubMedGoogle Scholar
• RAO PS, CAVANAGH D: Endotoxic shock in the baboon: some effects of glucocorticoid therapy. Surg. Forum (1970) 21:416–419.
   PubMedGoogle Scholar
• KADOWITZ PJ, YARD AC: Circulatory effects of hydrocortisone and protection against endotoxin shock in cats. Eur. Pharmacol. (1970) 9:311–318.
   PubMed Web of Science ®Google Scholar
• PRAGER R, KIRSH MM, DUNN E et al.: The benefits of corticosteroids in endotoxic shock. Ann. Thome. Surg. (1975) 19:142–152.
   PubMed Web of Science ®Google Scholar
• ROGERS J: Large doses of steroids in septicaemic shock. Br J. Urol. (1970) 42:742.
   PubMedGoogle Scholar
• KLASTERSKY J: Effectiveness of adrenal corticosteroids in the management of severe bacterial infections. Rev Eur. Etud. Biol. (1971) 16:413–417.
   PubMedGoogle Scholar
• WEITZMAN S, BERGER S: Clinical trial design in studies of corticosteroids for bacterial infections. Ann. Intern. Med. (1974) 81:36–42.
   PubMed Web of Science ®Google Scholar
• SCHUMER W: Steroids in the treatment ofclinical septic shock. Ann. Surg. (1976) 184:333–341.
   PubMed Web of Science ®Google Scholar
• NICHOLSON DP: Corticosteroids in the treatment of septic shock and the adult respiratory distress syndrome. Med. OM. North Am. (1983) 67:717–724.
   PubMed Web of Science ®Google Scholar
• LUCAS CE, LEDGERWOOD AM: The cardiopulmonary response to massive doses of steroids in patients with septic shock. Arch. Surg. (1984) 119:537–541.
   PubMed Web of Science ®Google Scholar
• SPRUNG CL, CARALIS PV, MARCIAL EH et al.: The effects of high-dose corticosteroids in patients with septic shock. A prospective, controlled study. N Engl. J. Med. (1984) 311:1137–1143.
   PubMed Web of Science ®Google Scholar
• HELLMAN A, ALESTIG K: High doses of corticosteroids in the treatment of septic shock. Acta Chir. Scam/. Suppl. (1985) 526:124–128.
   PubMedGoogle Scholar
• PUTTERMAN C: Corticosteroids in sepsis and septic shock: has the jury reached a verdict? Isr. J. Med. Sri. (1989) 25:332–338.
   PubMedGoogle Scholar
• CLEMMER TP, FISHER CJ JR, BONE RC et al.: Hypothermia in the sepsis syndrome and clinical outcome. The methylprednisolone severe sepsis study group. Grit. Care Med. (1992) 20:1395–1401.
   PubMed Web of Science ®Google Scholar
• SLOTMAN GJ, FISHER CJ JR, BONE RC, CLEMMER TP, METZ CA: Detrimental effects of high-dose methylprednisolone sodium succinate on serum concentrations of hepatic and renal function indicators in severe sepsis and septic shock. The methylprednisolone severe sepsis study group. Grit. Care Med. (1993) 21:191–195.
   PubMed Web of Science ®Google Scholar
• BRIEGEL J, KELLERMANN W, FORST H et al.: Low-dose hydrocortisone infusion attenuates the systemic inflammatory response syndrome. The phospholipase A2 study group. Clin Investig. (1994) 72:782–787.
   Google Scholar
• BOLLAERT PE, CHARPENTIER C, LEVY B et al.: Reversal of late septic shock with supraphysiologic doses of hydrocortisone. Crit. Care Med. (1998) 26:645–650.
   PubMed Web of Science ®Google Scholar
• ANNANE D: Corticosteroids for septic shock. Grit. Care Med. (2001) 29:S117–S120.
   Google Scholar
• BEUTLER B, KROCHIN N, MILSARK IW LUEDKE C, CERAMI A: Control of cachectin (tumor necrosis factor) synthesis: mechanisms of endotoxin resistance. Science (1986) 232:977-980. LPS-induced synthesis of TNF, earlier revealed as an endogenous mediator of LPS effects and known to be a relevant endpoint of LPS activation, is shown to be suppressed by pretreatment of macrophages with glucocorticoids hormones.
   Google Scholar
• ZIEGLER SF, WILSON CB, PERLMUTTER RM: Augmented expression of a myeloid-specific protein tyrosine kinase gene (hck) after macrophage activation. J. Exp. Med. (1988) 168:1801–1810.
   PubMed Web of Science ®Google Scholar
• CAMPBELL MA, SEFTON BM: Protein tyrosine phosphorylation is induced in murine B lymphocytes in response to stimulation with anti-immunoglobulin. EMBO J. (1990) 9:2125–2131.
   PubMed Web of Science ®Google Scholar
• WEINSTEIN SL, GOLD MR, DEFRANCO AL: Bacterial lipopolysaccharide stimulates protein tyrosine phosphorylation in macrophages. Proc. Nati Acad. Sri. USA (1991) 88:4148–4152.
   PubMed Web of Science ®Google Scholar
• DONG Z, O'BRIAN CA, FIDLER IJ: Activation of tumoricidal properties in macrophages by lipopolysaccharide requires protein-tyrosine kinase activity. J. Leukoc. Biol. (1993) 53:53–60.
   PubMed Web of Science ®Google Scholar
• BEATY CD, FRANKLIN TL, UEHARA Y, WILSON CB: Lipopolysaccharide-induced cytokine production in human monocytes: role of tyrosine phosphorylation in transmembrane signal transduction. Eur. Immurrol. (1994) 24:1278–1284.
   PubMed Web of Science ®Google Scholar
• NOVOGRODSKY A, VANICHKIN A, PATYA M etal.: Prevention of lipopolysaccharide-induced lethal toxicity by tyrosine kinase inhibitors. Science (1994) 264:1319–1322.
   Google Scholar
• •Tyrosine kinases, earlier implicated in LPS signaling, appear to be important for the lethal effect of LPS, insofar as tyrphostins (then relatively new tyrosine kinase inhibitors, are able to block lethality.
   Google Scholar
• LOWELL CA, BERTON G: Resistance to endotoxic shock and reduced neutrophil migration in mice deficient for the Src-family kinases Hck and Fgr. Proc. Nati Acad. Sri. USA (1998) 95:7580–7584.
   PubMed Web of Science ®Google Scholar
• STRIETER RM, REMICK DG, WARD PA et al.: Cellular and molecular regulation of tumor necrosis factor-alpha production by pentoxifylline. Biochem. Biophys. Res. Commun. (1988) 155:1230–1236.
   PubMed Web of Science ®Google Scholar
• HAN J, THOMPSON P, BEUTLER B: Dexamethasone and pentoxifylline inhibit endotoxin-induced cachectin/TNF synthesis at separate points in the signalling pathway. J. Exp. Med. (1990) 172:391–394.
   PubMed Web of Science ®Google Scholar
• •The inhibitory effects of GCs and PDE inhibitors are compared, and found to affect distinguishable elements within the LPS signaling pathway. In particular, GCs inhibit LPS-induced transcription and translation of the TNF gene and its mRNA product; PDE inhibitors have a selective effect on transcription.
   Google Scholar
• HAN J, BEUTLER B, HUEZ G: Complexregulation of TNF mRNA turnover in LPS-activated macrophages. Biochim. Biophy Acta (1991) 1090:22–28.
   PubMedGoogle Scholar
• DI PADOVA FE, BRADE H, BARCLAY GR et al: A broadly cross-protective monoclonal antibody binding to Escherichia coil and Salmonella lipopolysaccharides. Infect Immun. (1993) 61:3863–3872.
   PubMed Web of Science ®Google Scholar
• ANGUS DC, BIRMINGHAM MC, BALK RA et al.: E5 murine monoclonal antiendotoxin antibody in Gram-negative sepsis: a randomized controlled trial. E5 study investigators. JAMA (2000) 283:1723–1730.
   Google Scholar
• DERKX B, WITTES J, MCCLOSKEY R: Randomized, placebo-controlled trial of HA-1A, a human monoclonal antibody to endotoxin, in children with meningococcal septic shock. European Pediatric Meningococcal septic shock trial study Group. OM. Infect. Dis. (1999) 28:770–777.
   Google Scholar
• BONE RC, BALK RA, FEIN AM et al: Asecond large controlled clinical study of E5, a monoclonal antibody to endotoxin: results of a prospective, multicenter, randomized, controlled trial. The E5 sepsis study group. Grit. Care Med. (1995) 23:994–1006.
   PubMed Web of Science ®Google Scholar
• BIGATELLO LM, GREENE RE, SPRUNG CL et al: HA-1A in septic patients with ARDS: results from the pivotal trial. Inter]. Care Med. (1994) 20:328–334.
   PubMed Web of Science ®Google Scholar
• WORTEL CH, DER MOHLEN MA, VAN DEVENTER SJ etal.: Effectiveness of a human monoclonal anti-endotoxin antibody (HA-1A) in Gram-negative sepsis: relationship to endotoxin and cytokine levels. J. Infect. Dis. (1992) 166:1367–1374.
   Google Scholar
• ZIEGLER EJ, SMITH CR: Anti-endotoxinmonoclonal antibodies. N Engl. J. Med. (1992) 326:1165.
   PubMedGoogle Scholar
• WARREN HS, DANNER RL, MUNFORD RS: Anti-endotoxin monoclonal antibodies. N Engl. J. Med. (1992) 326:1153–1157.
   PubMed Web of Science ®Google Scholar
• BAUMGARTNER JD: Anti-endotoxin therapy and the management of sepsis. J. Antimicrob. Chemother. (1992) 29:360–363.
   PubMed Web of Science ®Google Scholar
• SCHEDEL I, DREIKHAUSEN U, NENTWIG B et al.: Treatment of Gram-negative septic shock with an immunoglobulin preparation: a prospective, randomized clinical trial. Crit. Care Med. (1991) 19:1104–1113.
   PubMed Web of Science ®Google Scholar
• GREENMAN RL, SCHEIN RM, MARTIN MA et al.: A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of Gram-negative sepsis. The XOMA Sepsis Study Group. JAMA (1991) 266:1097–1102.
   PubMed Web of Science ®Google Scholar
• ZIEGLER EJ, FISHER CJ JR, SPRUNG CL et al.: Treatment of Gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. A randomized, double-blind, placebo-controlled trial. The HA-1A Sepsis Study Group. N Engl. J. Med. (1991) 324:429–436.
   Google Scholar
• GREENBERG RN, WILSON KM, KUNZ AY, WEDEL NI, GORELICK KJ: Randomized, double-blind Phase II study of anti-endotoxin antibody (E5) as adjuvant therapy in humans with serious Gram-negative infections. Frog. OM. Biol. Res. (1991) 367:179–186.
   PubMedGoogle Scholar
• ZIEGLER EJ: Immunological intervention in endotoxin shock. Frog. Clin Biol. Res. (1988) 272:319–325.
   PubMedGoogle Scholar
• ZIEGLER EJ, MCCUTCHAN JA, FIERER J etal.: Treatment of Gram-negative bacteremia and shock with human antiserum to a mutant Escherichia coli. N Engl. J. Med. (1982) 307:1225–1230.
   Google Scholar
• MCCUTCHAN JA, ZIEGLER EJ, BRAUDE Al: Treatment of Gram-negative bacteremia with antiserum to core glycolipid II. A controlled trial of antiserum in patients with bacteremia. Eur. J. Cancer (1979) 15(Suppl.):77–80.
   Google Scholar
• LEVIN M, QUINT PA, GOLDSTEIN B et al.: Recombinant bactericidal/permeability-increasing protein (rBPI21) as adjunctive treatment for children with severe meningococcal sepsis: a randomised trial. rBPI21 Meningococcal Sepsis Study Group. Lancet (2000) 356:961–967.
   Google Scholar
• VERBON A, DEKKERS PE, TEN HOVE T et al: IC14, an anti-CD14 antibody, inhibits endotoxin-mediated symptoms and inflammatory responses in humans. J. Immuria. (2001) 166:3599–3605.
   PubMed Web of Science ®Google Scholar
• TAKAYAMA K, QURESHI N, BEUTLER B, KIRKLAND TN: Diphosphoryl lipid A from Rhodopseudomonas spaeroides ATCC 17023 blocks induction of cachectin in macrophages by lipopolysaccharide. Infer. Immun. (1989) 57:1336–1338.
   PubMed Web of Science ®Google Scholar
• •The relatively non-toxic LPS of Rhodopseudomonar sphaeroides is shown to antagonize TNF production induced by toxic LPS, derived from E. coll. This observation suggested competition at the level of a receptor, though the identity of the receptor remained unclear.
   Google Scholar
• KAWATA T, BRISTOL JR, ROSE JR et al: Anti-endotoxin activity of a novel synthetic lipid A analog. Frog. OM. Biol. Res. (1995) 392:499–509.
   PubMedGoogle Scholar
• ROSE JR, CHRIST WJ, BRISTOL JR, KAWATA T, ROSSIGNOL DP: Agonistic and antagonistic activities of bacterially derived Rhodobacter sphaeroides lipid A: comparison with activities of synthetic material of the proposed structure and analogs. Infect Immun. (1995) 63:833–839.
   PubMed Web of Science ®Google Scholar
• KOBAYASHI S, KAWATA T, KIMURA A et al.: Suppression of murine endotoxin response by E5531, a novel synthetic lipid A antagonist. Antimicrob. Agents Chemother. (1998) 42:2824–2829.
   PubMed Web of Science ®Google Scholar
• KAWATA T, BRISTOL JR, ROSSIGNOL DP et al: E5531, a synthetic non-toxic lipid A derivative blocks the immunobiological activities of lipopolysaccharide. Br J. Pharmacal. (1999) 127:853–862.
   PubMed Web of Science ®Google Scholar
• HAWKINS LD, ISHIZAKA ST, MCGUINNESS P et al.: A novel class of endotoxin receptor agonists with simplified structure, Toll-like receptor 4-dependent immunostimulatory action and adjuvant activity. J. Pharmacal. Exp. Ther. (2002) 300:655–661.
   PubMed Web of Science ®Google Scholar
• MACELA A, STULIK J, HERNYCHOVA L et al.: The immune response against Francisella tularensis live vaccine strain in Lpsn and Lpsd mice. FEMS Immune]. Med. Microbiol. (1996) 13:235–238.
   PubMed Web of Science ®Google Scholar
• HAGBERG L, HULL R, HULLS et al: Difference in susceptibility to Gram-negative urinary tract infection between C3H/HeJ and C3H/HeN mice. Infect. Immun. (1984) 46:839-844. ma. PARIS MM, HICKEY SM, USCHER MI et al: Effect of dexamethasone on therapy of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis. Antimicrob. Agents Chemother. (1994) 38:1320–1324.
   Google Scholar
• COOKE KR, GERBITZ A, CRAWFORD JM et al.: LPS antagonism reduces graft- versus-host disease and preserves graft- versus-leukemia activity after experimental bone marrow transplantation. Chu. Invest. (2001) 107:1581–1589.
   PubMed Web of Science ®Google Scholar
• BAGHAI M, OSMON DR, WOLK DM et al.: Fatal sepsis in a patient with rheumatoid arthritis treated with etanercept. Mayo Chu. Proc. (2001) 76:653–656.
   PubMed Web of Science ®Google Scholar
• KEANE J, GERSHON S, WISE RP et a/.: Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl. I Med. (2001) 345:1098–1104.
   Google Scholar
• WARRIS A, BJORNEKLETT A, GAUSTAD P: Invasive pulmonary aspergillosis associated with infliximab therapy. N. Engl. J. Med. (2001) 344:1099–1100.
   PubMed Web of Science ®Google Scholar