1,129
Views
20
CrossRef citations to date
0
Altmetric
Original Article

Soluble ST2, a modulator of the inflammatory response, in preterm and term labor

, , , , , , , , & show all
Pages 111-121 | Received 21 Dec 2012, Accepted 16 May 2013, Published online: 13 Nov 2013

References

  • Romero R, Mazor M, Wu YK, et al. Infection in the pathogenesis of preterm labor. Semin Perinatol 1988;12:262–79
  • Kullander S. Fever and parturition. An experimental study in rabbits. Acta Obstet Gynecol Scand Suppl 1977;66:77–85
  • Bobitt JR, Hayslip CC, Damato JD. Amniotic fluid infection as determined by transabdominal amniocentesis in patients with intact membranes in premature labor. Am J Obstet Gynecol 1981;140:947–52
  • Cassell GH, Davis RO, Waites KB, et al. Isolation of Mycoplasma hominis and Ureaplasma urealyticum from amniotic fluid at 16–20 weeks of gestation: potential effect on outcome of pregnancy. Sex Transm Dis 1983;10:294–302
  • Minkoff H. Prematurity: infection as an etiologic factor. Obstet Gynecol 1983;62:137–44
  • Hameed C, Tejani N, Verma UL, Archbald F. Silent chorioamnionitis as a cause of preterm labor refractory to tocolytic therapy. Am J Obstet Gynecol 1984;149:726–30
  • Wahbeh CJ, Hill GB, Eden RD, Gall SA. Intra-amniotic bacterial colonization in premature labor. Am J Obstet Gynecol 1984;148:739–43
  • Leigh J, Garite TJ. Amniocentesis and the management of premature labor. Obstet Gynecol 1986;67:500–6
  • Gravett MG, Hummel D, Eschenbach DA, Holmes KK. Preterm labor associated with subclinical amniotic fluid infection and with bacterial vaginosis. Obstet Gynecol 1986;67:229–37
  • Romero R, Quintero R, Oyarzun E, et al. Intraamniotic infection and the onset of labor in preterm premature rupture of the membranes. Am J Obstet Gynecol 1988;159:661–6
  • Romero R, Sirtori M, Oyarzun E, et al. Infection and labor. V. Prevalence, microbiology, and clinical significance of intraamniotic infection in women with preterm labor and intact membranes. Am J Obstet Gynecol 1989;161:817–24
  • Skoll MA, Moretti ML, Sibai BM. The incidence of positive amniotic fluid cultures in patients preterm labor with intact membranes. Am J Obstet Gynecol 1989;161:813–16
  • Dombroski RA, Woodard DS, Harper MJ, Gibbs RS. A rabbit model for bacteria-induced preterm pregnancy loss. Am J Obstet Gynecol 1990;163:1938–43
  • Romero R, Avila C, Santhanam U, Sehgal PB. Amniotic fluid interleukin 6 in preterm labor. Association with infection. J Clin Invest 1990;85:1392–400
  • Romero R, Mazor M, Tartakovsky B. Systemic administration of interleukin-1 induces preterm parturition in mice. Am J Obstet Gynecol 1991;165:969–71
  • Romero R, Quintero R, Nores J, et al. Amniotic fluid white blood cell count: a rapid and simple test to diagnose microbial invasion of the amniotic cavity and predict preterm delivery. Am J Obstet Gynecol 1991;165:821–30
  • Romero R, Mazor M, Brandt F, et al. Interleukin-1 alpha and interleukin-1 beta in preterm and term human parturition. Am J Reprod Immunol 1992;27:117–23
  • Gibbs RS, Romero R, Hillier SL, et al. A review of premature birth and subclinical infection. Am J Obstet Gynecol 1992;166:1515–28
  • Coultrip LL, Grossman JH. Evaluation of rapid diagnostic tests in the detection of microbial invasion of the amniotic cavity. Am J Obstet Gynecol 1992;167:1231–42
  • Romero R, Yoon BH, Mazor M, et al. The diagnostic and prognostic value of amniotic fluid white blood cell count, glucose, interleukin-6, and gram stain in patients with preterm labor and intact membranes. Am J Obstet Gynecol 1993;169:805–16
  • Romero R, Mazor M, Munoz H, et al. The preterm labor syndrome. Ann N Y Acad Sci 1994;734:414–29
  • Fidel PL Jr, Romero R, Wolf N, et al. Systemic and local cytokine profiles in endotoxin-induced preterm parturition in mice. Am J Obstet Gynecol 1994;170:1467–75
  • Gravett MG, Witkin SS, Haluska GJ, et al. An experimental model for intraamniotic infection and preterm labor in rhesus monkeys. Am J Obstet Gynecol 1994;171:1660–7
  • Coultrip LL, Lien JM, Gomez R, et al. The value of amniotic fluid interleukin-6 determination in patients with preterm labor and intact membranes in the detection of microbial invasion of the amniotic cavity. Am J Obstet Gynecol 1994;171:901–11
  • Gomez R, Ghezzi F, Romero R, et al. Premature labor and intra-amniotic infection. Clinical aspects and role of the cytokines in diagnosis and pathophysiology. Clin Perinatol 1995;22:281–342
  • Hirsch E, Saotome I, Hirsh D. A model of intrauterine infection and preterm delivery in mice. Am J Obstet Gynecol 1995;172:1598–603
  • Horowitz S, Mazor M, Romero R, et al. Infection of the amniotic cavity with Ureaplasma urealyticum in the midtrimester of pregnancy. J Reprod Med 1995;40:375–9
  • Gravett MG, Haluska GJ, Cook MJ, Novy MJ. Fetal and maternal endocrine responses to experimental intrauterine infection in rhesus monkeys. Am J Obstet Gynecol 1996;174:1725–31; discussion 1731–1723
  • Yoon BH, Yang SH, Jun JK, et al. Maternal blood C-reactive protein, white blood cell count, and temperature in preterm labor: a comparison with amniotic fluid white blood cell count. Obstet Gynecol 1996;87:231–7
  • Goncalves LF, Chaiworapongsa T, Romero R. Intrauterine infection and prematurity. Ment Retard Dev Disabil Res Rev 2002;8:3–13
  • Gibbs RS, McDuffie RS Jr, Kunze M, et al. Experimental intrauterine infection with Prevotella bivia in New Zealand White rabbits. Am J Obstet Gynecol 2004;190:1082–6
  • Romero R, Espinoza J, Goncalves LF, et al. The role of inflammation and infection in preterm birth. Semin Reprod Med 2007;25:21–39
  • Novy MJ, Duffy L, Axthelm MK, et al. Ureaplasma parvum or Mycoplasma hominis as sole pathogens cause chorioamnionitis, preterm delivery, and fetal pneumonia in rhesus macaques. Reprod Sci 2009;16:56–70
  • Kalan AM, Simhan HN. Mid-trimester cervical inflammatory milieu and sonographic cervical length. Am J Obstet Gynecol 2010;203:126 e121–5
  • Trivedi S, Joachim M, McElrath T, et al. Fetal-placental inflammation, but not adrenal activation, is associated with extreme preterm delivery. Am J Obstet Gynecol 2012;206:236 e231–8
  • Kiefer DG, Keeler SM, Rust O, et al. Amniotic fluid inflammatory score is associated with pregnancy outcome in patients with mid trimester short cervix. Am J Obstet Gynecol 2012;206:68 e61–6
  • Hsu TY, Lin H, Lan KC, et al. High interleukin-16 concentrations in the early second trimester amniotic fluid: an independent predictive marker for preterm birth. J Matern Fetal Neonatal Med 2013;26:285–9
  • Park CW, Hyun Yoon B, Shin Park J, Kwan Jun J. An elevated maternal serum c-reactive protein in the context of intra-amniotic inflammation is an indicator that the development of amnionitis, an intense fetal and AF inflammatory response are likely in patients with preterm labor: clinical implications. J Matern Fetal Neonatal Med 2013;26:847–53
  • Romero R, Gomez R, Chaiworapongsa T, et al. The role of infection in preterm labour and delivery. Paediatr Perinat Epidemiol 2001;15:41–56
  • Watts DH, Krohn MA, Hillier SL, Eschenbach DA. The association of occult amniotic fluid infection with gestational age and neonatal outcome among women in preterm labor. Obstet Gynecol 1992;79:351–7
  • Gomez R, Romero R, Nien JK, et al. A short cervix in women with preterm labor and intact membranes: a risk factor for microbial invasion of the amniotic cavity. Am J Obstet Gynecol 2005;192:678–89
  • Pao CC, Kao SM, Wang HC, Lee CC. Intraamniotic detection of Chlamydia trachomatis deoxyribonucleic acid sequences by polymerase chain reaction. Am J Obstet Gynecol 1991;164:1295–9
  • Jalava J, Mantymaa ML, Ekblad U, et al. Bacterial 16S rDNA polymerase chain reaction in the detection of intra-amniotic infection. Br J Obstet Gynaecol 1996;103:664–9
  • Hitti J, Riley DE, Krohn MA, et al. Broad-spectrum bacterial rDNA polymerase chain reaction assay for detecting amniotic fluid infection among women in premature labor. Clin Infect Dis 1997;24:1228–32
  • Gravett MG, Novy MJ, Rosenfeld RG, et al. Diagnosis of intra-amniotic infection by proteomic profiling and identification of novel biomarkers. JAMA 2004;292:462–9
  • Miralles R, Hodge R, McParland PC, et al. Relationship between antenatal inflammation and antenatal infection identified by detection of microbial genes by polymerase chain reaction. Pediatr Res 2005;57:570–7
  • DiGiulio DB, Romero R, Kusanovic JP, et al. Prevalence and diversity of microbes in the amniotic fluid, the fetal inflammatory response, and pregnancy outcome in women with preterm pre-labor rupture of membranes. Am J Reprod Immunol 2010;64:38–57
  • Romero R, Brody DT, Oyarzun E, et al. Infection and labor. III. Interleukin-1: a signal for the onset of parturition. Am J Obstet Gynecol 1989;160:1117–23
  • Romero R, Sepulveda W, Kenney JS, et al. Interleukin 6 determination in the detection of microbial invasion of the amniotic cavity. Ciba Found Symp 1992;167:205–20; discussion 220–203
  • Romero R, Mazor M, Sepulveda W, et al. Tumor necrosis factor in preterm and term labor. Am J Obstet Gynecol 1992;166:1576–87
  • McDuffie RS, Jr Sherman MP, Gibbs RS. Amniotic fluid tumor necrosis factor-alpha and interleukin-1 in a rabbit model of bacterially induced preterm pregnancy loss. Am J Obstet Gynecol 1992;167:1583–8
  • Romero R, Yoon BH, Kenney JS, et al. Amniotic fluid interleukin-6 determinations are of diagnostic and prognostic value in preterm labor. Am J Reprod Immunol 1993;30:167–83
  • Romero R, Gomez R, Galasso M, et al. Macrophage inflammatory protein-1 alpha in term and preterm parturition: effect of microbial invasion of the amniotic cavity. Am J Reprod Immunol 1994;32:108–13
  • Yoon BH, Romero R, Kim CJ, et al. Amniotic fluid interleukin-6: a sensitive test for antenatal diagnosis of acute inflammatory lesions of preterm placenta and prediction of perinatal morbidity. Am J Obstet Gynecol 1995;172:960–70
  • Andrews WW, Hauth JC, Goldenberg RL, et al. Amniotic fluid interleukin-6: correlation with upper genital tract microbial colonization and gestational age in women delivered after spontaneous labor versus indicated delivery. Am J Obstet Gynecol 1995;173:606–12
  • Fortunato SJ, Menon RP, Swan KF, Menon R. Inflammatory cytokine (interleukins 1, 6 and 8 and tumor necrosis factor-alpha) release from cultured human fetal membranes in response to endotoxic lipopolysaccharide mirrors amniotic fluid concentrations. Am J Obstet Gynecol 1996;174:1855–61; discussion 1861–1852
  • Kara M, Ozden S, Arioglu P, Cetin A. The significance of amniotic fluid interleukin-6 levels in preterm labour. Aust N Z J Obstet Gynaecol 1998;38:403–6
  • Arntzen KJ, Kjollesdal AM, Halgunset J, et al. TNF, IL-1, IL-6, IL-8 and soluble TNF receptors in relation to chorioamnionitis and premature labor. J Perinat Med 1998;26:17–26
  • Maymon E, Ghezzi F, Edwin SS, et al. The tumor necrosis factor alpha and its soluble receptor profile in term and preterm parturition. Am J Obstet Gynecol 1999;181:1142–8
  • Baud O, Emilie D, Pelletier E, et al. Amniotic fluid concentrations of interleukin-1beta, interleukin-6 and TNF-alpha in chorioamnionitis before 32 weeks of gestation: histological associations and neonatal outcome. Br J Obstet Gynaecol 1999;106:72–7
  • Wenstrom KD, Andrews WW, Hauth JC, et al. Elevated second-trimester amniotic fluid interleukin-6 levels predict preterm delivery. Am J Obstet Gynecol 1998;178:546–50
  • Keelan JA, Marvin KW, Sato TA, et al. Cytokine abundance in placental tissues: evidence of inflammatory activation in gestational membranes with term and preterm parturition. Am J Obstet Gynecol 1999;181:1530–6
  • Zaga-Clavellina V, Garcia-Lopez G, Flores-Herrera H, et al. In vitro secretion profiles of interleukin (IL)-1beta, IL-6, IL-8, IL-10, and TNF alpha after selective infection with Escherichia coli in human fetal membranes. Reprod Biol Endocrinol 2007;5:46
  • Chaiworapongsa T, Erez O, Kusanovic JP, et al. Amniotic fluid heat shock protein 70 concentration in histologic chorioamnionitis, term and preterm parturition. J Matern Fetal Neonatal Med 2008;21:449–61
  • Krolak-Olejnik B, Olejnik I. Late-preterm cesarean delivery and chemokines concentration in the umbilical cord blood of neonates. J Matern Fetal Neonatal Med 2012;25:1810–13
  • Kusanovic JP, Romero R, Chaiworapongsa T, et al. Amniotic fluid sTREM-1 in normal pregnancy, spontaneous parturition at term and preterm, and intra-amniotic infection/inflammation. J Matern Fetal Neonatal Med 2010;23:34–47
  • Kacerovsky M, Musilova I, Khatibi A, et al. Intraamniotic inflammatory response to bacteria: analysis of multiple amniotic fluid proteins in women with preterm prelabor rupture of membranes. J Matern Fetal Neonatal Med 2012;25:2014–19
  • Hassanein SM, El-Farrash RA, Hafez HM, et al. Cord blood interleukin-6 and neonatal morbidities among preterm infants with PCR-positive Ureaplasma urealyticum. J Matern Fetal Neonatal Med 2012;25:2106–10
  • Vaisbuch E, Romero R, Gomez R, et al. An elevated fetal interleukin-6 concentration can be observed in fetuses with anemia due to Rh alloimmunization: implications for the understanding of the fetal inflammatory response syndrome. J Matern Fetal Neonatal Med 2011;24:391–6
  • Tsiartas P, Kacerovsky M, Musilova I, et al. The association between histological chorioamnionitis, funisitis and neonatal outcome in women with preterm prelabor rupture of membranes. J Matern Fetal Neonatal Med 2013;Apr 16 [e-pub ahead of print]
  • Kacerovsky M, Cobo T, Andrys C, et al. The fetal inflammatory response in subgroups of women with preterm prelabor rupture of the membranes. J Matern Fetal Neonatal Med 2013;26:795–801
  • Martinelli P, Sarno L, Maruotti GM, Paludetto R. Chorioamnionitis and prematurity: a critical review. J Matern Fetal Neonatal Med 2012;25:29–31
  • Sadowsky DW, Adams KM, Gravett MG, et al. Preterm labor is induced by intraamniotic infusions of interleukin-1beta and tumor necrosis factor-alpha but not by interleukin-6 or interleukin-8 in a nonhuman primate model. Am J Obstet Gynecol 2006;195:1578–89
  • Marconi C, de Andrade Ramos BR, Peracoli JC, et al. Amniotic fluid interleukin-1 beta and interleukin-6, but not interleukin-8 correlate with microbial invasion of the amniotic cavity in preterm labor. Am J Reprod Immunol 2011;65:549–56
  • Romero R, Tartakovsky B. The natural interleukin-1 receptor antagonist prevents interleukin-1-induced preterm delivery in mice. Am J Obstet Gynecol 1992;167:1041–5
  • Romero R, Sepulveda W, Mazor M, et al. The natural interleukin-1 receptor antagonist in term and preterm parturition. Am J Obstet Gynecol 1992;167:863–72
  • Romero R, Manogue KR, Mitchell MD, et al. Infection and labor. IV. Cachectin-tumor necrosis factor in the amniotic fluid of women with intraamniotic infection and preterm labor. Am J Obstet Gynecol 1989;161:336–41
  • Bry K, Hallman M. Transforming growth factor-beta 2 prevents preterm delivery induced by interleukin-1 alpha and tumor necrosis factor-alpha in the rabbit. Am J Obstet Gynecol 1993;168:1318–22
  • Baumann P, Romero R, Berry S, et al. Evidence of participation of the soluble tumor necrosis factor receptor I in the host response to intrauterine infection in preterm labor. Am J Reprod Immunol 1993;30:184–93
  • Fortunato SJ, Menon R, Lombardi SJ. Role of tumor necrosis factor-alpha in the premature rupture of membranes and preterm labor pathways. Am J Obstet Gynecol 2002;187:1159–62
  • Lonergan M, Aponso D, Marvin KW, et al. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), TRAIL receptors, and the soluble receptor osteoprotegerin in human gestational membranes and amniotic fluid during pregnancy and labor at term and preterm. J Clin Endocrinol Metab 2003;88:3835–44
  • Cherouny PH, Pankuch GA, Romero R, et al. Neutrophil attractant/activating peptide-1/interleukin-8: association with histologic chorioamnionitis, preterm delivery, and bioactive amniotic fluid leukoattractants. Am J Obstet Gynecol 1993;169:1299–303
  • Saito S, Kasahara T, Kato Y, et al. Elevation of amniotic fluid interleukin 6 (IL-6), IL-8 and granulocyte colony stimulating factor (G-CSF) in term and preterm parturition. Cytokine 1993;5:81–8
  • Puchner T, Egarter C, Wimmer C, et al. Amniotic fluid interleukin-8 as a marker for intraamniotic infection. Arch Gynecol Obstet 1993;253:9–14
  • Dudley DJ, Trautman MS, Mitchell MD. Inflammatory mediators regulate interleukin-8 production by cultured gestational tissues: evidence for a cytokine network at the chorio-decidual interface. J Clin Endocrinol Metab 1993;76:404–10
  • Fortunato SJ, Menon R, Swan KF. Amniochorion: a source of interleukin-8. Am J Reprod Immunol 1995;34:156–62
  • Tanaka Y, Narahara H, Takai N, et al. Interleukin-1beta and interleukin-8 in cervicovaginal fluid during pregnancy. Am J Obstet Gynecol 1998;179:644–9
  • Hsu CD, Meaddough E, Aversa K, et al. Elevated amniotic fluid levels of leukemia inhibitory factor, interleukin 6, and interleukin 8 in intra-amniotic infection. Am J Obstet Gynecol 1998;179:1267–70
  • Laham N, Brennecke SP, Rice GE. Interleukin-8 release from human gestational tissue explants: effects of gestation, labor, and chorioamnionitis. Biol Reprod 1999;61:823–7
  • Dowd J, Laham N, Rice G, et al. Elevated interleukin-8 concentrations in cervical secretions are associated with preterm labour. Gynecol Obstet Invest 2001;51:165–8
  • Witt A, Berger A, Gruber CJ, et al. IL-8 concentrations in maternal serum, amniotic fluid and cord blood in relation to different pathogens within the amniotic cavity. J Perinat Med 2005;33:22–6
  • Jacobsson B, Mattsby-Baltzer I, Hagberg H. Interleukin-6 and interleukin-8 in cervical and amniotic fluid: relationship to microbial invasion of the chorioamniotic membranes. BJOG 2005;112:719–24
  • Yoneda S, Sakai M, Sasaki Y, et al. Interleukin-8 and glucose in amniotic fluid, fetal fibronectin in vaginal secretions and preterm labor index based on clinical variables are optimal predictive markers for preterm delivery in patients with intact membranes. J Obstet Gynaecol Res 2007;33:38–44
  • Kendal-Wright CE, Hubbard D, Gowin-Brown J, Bryant-Greenwood GD. Stretch and inflammation-induced Pre-B cell colony-enhancing factor (PBEF/Visfatin) and Interleukin-8 in amniotic epithelial cells. Placenta 2010;31:665–74
  • Yoneda S, Shiozaki A, Yoneda N, et al. Prediction of exact delivery time in patients with preterm labor and intact membranes at admission by amniotic fluid interleukin-8 level and preterm labor index. J Obstet Gynaecol Res 2011;37:861–6
  • Jacobsson B, Holst RM, Wennerholm UB, et al. Monocyte chemotactic protein-1 in cervical and amniotic fluid: relationship to microbial invasion of the amniotic cavity, intra-amniotic inflammation, and preterm delivery. Am J Obstet Gynecol 2003;189:1161–7
  • Esplin MS, Romero R, Chaiworapongsa T, et al. Monocyte chemotactic protein-1 is increased in the amniotic fluid of women who deliver preterm in the presence or absence of intra-amniotic infection. J Matern Fetal Neonatal Med 2005;17:365–73
  • Esplin MS, Peltier MR, Hamblin S, et al. Monocyte chemotactic protein-1 expression is increased in human gestational tissues during term and preterm labor. Placenta 2005;26:661–71
  • Diamond AK, Sweet LM, Oppenheimer KH, et al. Modulation of monocyte chemotactic protein-1 expression during lipopolysaccharide-induced preterm delivery in the pregnant mouse. Reprod Sci 2007;14:548–59
  • Shynlova O, Tsui P, Dorogin A, Lye SJ. Monocyte chemoattractant protein-1 (CCL-2) integrates mechanical and endocrine signals that mediate term and preterm labor. J Immunol 2008;181:1470–9
  • Dudley DJ, Spencer S, Edwin S, Mitchell MD. Regulation of human decidual cell macrophage inflammatory protein-1 alpha (MIP-1 alpha) production by inflammatory cytokines. Am J Reprod Immunol 1995;34:231–5
  • Dudley DJ, Hunter C, Mitchell MD, Varner MW. Elevations of amniotic fluid macrophage inflammatory protein-1 alpha concentrations in women during term and preterm labor. Obstet Gynecol 1996;87:94–8
  • Cohen J, Ghezzi F, Romero R, et al. GRO alpha in the fetomaternal and amniotic fluid compartments during pregnancy and parturition. Am J Reprod Immunol 1996;35:23–9
  • Hsu CD, Meaddough E, Aversa K, Copel JA. The role of amniotic fluid L-selectin, GRO-alpha, and interleukin-8 in the pathogenesis of intraamniotic infection. Am J Obstet Gynecol 1998;178:428–32
  • Krolak-Olejnik B, Beck B, Olejnik I. Umbilical serum concentrations of chemokines (RANTES and MGSA/GRO-alpha) in preterm and term neonates. Pediatr Int 2006;48:586–90
  • Romero R, Salafia CM, Athanassiadis AP, et al. The relationship between acute inflammatory lesions of the preterm placenta and amniotic fluid microbiology. Am J Obstet Gynecol 1992;166:1382–8
  • Hillier SL, Witkin SS, Krohn MA, et al. The relationship of amniotic fluid cytokines and preterm delivery, amniotic fluid infection, histologic chorioamnionitis, and chorioamnion infection. Obstet Gynecol 1993;81:941–8
  • Steel JH, O'Donoghue K, Kennea NL, et al. Maternal origin of inflammatory leukocytes in preterm fetal membranes, shown by fluorescence in situ hybridisation. Placenta 2005;26:672–7
  • Aquino TI, Zhang J, Kraus FT, et al. Subchorionic fibrin cultures for bacteriologic study of the placenta. Am J Clin Pathol 1984;81:482–6
  • Pankuch GA, Appelbaum PC, Lorenz RP, et al. Placental microbiology and histology and the pathogenesis of chorioamnionitis. Obstet Gynecol 1984;64:802–6
  • Chellam VG, Rushton DI. Chorioamnionitis and funiculitis in the placentas of 200 births weighing less than 2.5 kg. Br J Obstet Gynaecol 1985;92:808–14
  • Hillier SL, Martius J, Krohn M, et al. A case-control study of chorioamnionic infection and histologic chorioamnionitis in prematurity. N Engl J Med 1988;319:972–8
  • Gomez R, Romero R, Ghezzi F, et al. The fetal inflammatory response syndrome. Am J Obstet Gynecol 1998;179:194–202
  • Pacora P, Chaiworapongsa T, Maymon E, et al. Funisitis and chorionic vasculitis: the histological counterpart of the fetal inflammatory response syndrome. J Matern Fetal Neonatal Med 2002;11:18–25
  • Gotsch F, Romero R, Kusanovic JP, et al. The fetal inflammatory response syndrome. Clin Obstet Gynecol 2007;50:652–83
  • Romero R, Espinoza J, Goncalves LF, et al. Fetal cardiac dysfunction in preterm premature rupture of membranes. J Matern Fetal Neonatal Med 2004;16:146–57
  • Romero R, Soto E, Berry SM, et al. Blood pH and gases in fetuses in preterm labor with and without systemic inflammatory response syndrome. J Matern Fetal Neonatal Med 2012;25:1160–70
  • Chaiworapongsa T, Romero R, Berry SM, et al. The role of granulocyte colony-stimulating factor in the neutrophilia observed in the fetal inflammatory response syndrome. J Perinat Med 2011;39:653–66
  • Yoon BH, Romero R, Park JS, et al. The relationship among inflammatory lesions of the umbilical cord (funisitis), umbilical cord plasma interleukin 6 concentration, amniotic fluid infection, and neonatal sepsis. Am J Obstet Gynecol 2000;183:1124–9
  • Baltimore RS. Neonatal sepsis: epidemiology and management. Paediatr Drugs 2003;5:723–40
  • Wolfs TG, Jellema RK, Turrisi G, et al. Inflammation-induced immune suppression of the fetus: a potential link between chorioamnionitis and postnatal early onset sepsis. J Matern Fetal Neonatal Med 2012;25:8–11
  • Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr 1978;92:529–34
  • Yoon BH, Jun JK, Romero R, et al. Amniotic fluid inflammatory cytokines (interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha), neonatal brain white matter lesions, and cerebral palsy. Am J Obstet Gynecol 1997;177:19–26
  • Kuperman AA, Kenet G, Papadakis E, Brenner B. Intraventricular hemorrhage in preterm infants: coagulation perspectives. Semin Thromb Hemost 2011;37:730–6
  • Yoon BH, Romero R, Yang SH, et al. Interleukin-6 concentrations in umbilical cord plasma are elevated in neonates with white matter lesions associated with periventricular leukomalacia. Am J Obstet Gynecol 1996;174:1433–40
  • Yoon BH, Kim CJ, Romero R, et al. Experimentally induced intrauterine infection causes fetal brain white matter lesions in rabbits. Am J Obstet Gynecol 1997;177:797–802
  • Yoon BH, Romero R, Kim CJ, et al. High expression of tumor necrosis factor-alpha and interleukin-6 in periventricular leukomalacia. Am J Obstet Gynecol 1997;177:406–11
  • Martinez E, Figueroa R, Garry D, et al. Elevated amniotic fluid interleukin-6 as a predictor of neonatal periventricular leukomalacia and intraventricular hemorrhage. J Matern Fetal Investig 1998;8:101–7
  • Yoon BH, Romero R, Park JS, et al. Fetal exposure to an intra-amniotic inflammation and the development of cerebral palsy at the age of three years. Am J Obstet Gynecol 2000;182:675–81
  • Moon JB, Kim JC, Yoon BH, et al. Amniotic fluid matrix metalloproteinase-8 and the development of cerebral palsy. J Perinat Med 2002;30:301–6
  • Willoughby RE, Jr Nelson KB. Chorioamnionitis and brain injury. Clin Perinatol 2002;29:603–21
  • Yoon BH, Park CW, Chaiworapongsa T. Intrauterine infection and the development of cerebral palsy. BJOG 2003;110:124–7
  • Nelson KB, Grether JK, Dambrosia JM, et al. Neonatal cytokines and cerebral palsy in very preterm infants. Pediatr Res 2003;53:600–7
  • Bashiri A, Burstein E, Mazor M. Cerebral palsy and fetal inflammatory response syndrome: a review. J Perinat Med 2006;34:5–12
  • Andrews WW, Cliver SP, Biasini F, et al. Early preterm birth: association between in utero exposure to acute inflammation and severe neurodevelopmental disability at 6 years of age. Am J Obstet Gynecol 2008;198:466–e1--11
  • Nelson KB. Infection in pregnancy and cerebral palsy. Dev Med Child Neurol 2009;51:253–4
  • Leviton A, Allred EN, Kuban KC, et al. Microbiologic and histologic characteristics of the extremely preterm infant's placenta predict white matter damage and later cerebral palsy. the ELGAN study. Pediatr Res 2010;67:95–101
  • Allin MP, Kontis D, Walshe M, et al. White matter and cognition in adults who were born preterm. PLoS One 2011;6:e24525
  • Kalpakidou AK, Allin MP, Walshe M, et al. Neonatal brain injury and neuroanatomy of memory processing following very preterm birth in adulthood: an fMRI study. PLoS One 2012;7:e34858
  • Ghezzi F, Gomez R, Romero R, et al. Elevated interleukin-8 concentrations in amniotic fluid of mothers whose neonates subsequently develop bronchopulmonary dysplasia. Eur J Obstet Gynecol Reprod Biol 1998;78:5–10
  • Yoon BH, Romero R, Kim KS, et al. A systemic fetal inflammatory response and the development of bronchopulmonary dysplasia. Am J Obstet Gynecol 1999;181:773–9
  • Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001;163:1723–9
  • Van Marter LJ, Dammann O, Allred EN, et al. Chorioamnionitis, mechanical ventilation, and postnatal sepsis as modulators of chronic lung disease in preterm infants. J Pediatr 2002;140:171–6
  • Mittendorf R, Covert R, Montag AG, et al. Special relationships between fetal inflammatory response syndrome and bronchopulmonary dysplasia in neonates. J Perinat Med 2005;33:428–34
  • Baraldi E, Filippone M. Chronic lung disease after premature birth. N Engl J Med 2007;357:1946–55
  • Murthy V, Kennea NL. Antenatal infection/inflammation and fetal tissue injury. Best Pract Res Clin Obstet Gynaecol 2007;21:479–89
  • Cutz E, Chiasson D. Chronic lung disease after premature birth. N Engl J Med 2008;358:743–5; author reply 745–746
  • Lee J, Oh KJ, Yang HJ, et al. The importance of intra-amniotic inflammation in the subsequent development of atypical chronic lung disease. J Matern Fetal Neonatal Med 2009;22:917–23
  • Chen J, Smith LE. Retinopathy of prematurity. Angiogenesis 2007;10:133–40
  • Harrell SN, Brandon DH. Retinopathy of prematurity: the disease process, classifications, screening, treatment, and outcomes. Neonatal Netw 2007;26:371–8
  • Sood BG, Madan A, Saha S, et al. Perinatal systemic inflammatory response syndrome and retinopathy of prematurity. Pediatr Res 2010;67:394–400
  • Romero R, Gomez R, Ghezzi F, et al. A fetal systemic inflammatory response is followed by the spontaneous onset of preterm parturition. Am J Obstet Gynecol 1998;179:186–93
  • Medzhitov R, Janeway C Jr. The Toll receptor family and microbial recognition. Trends Microbiol 2000;8:452–6
  • Beutler B, Hoebe K, Du X, Ulevitch RJ. How we detect microbes and respond to them: the Toll-like receptors and their transducers. J Leukoc Biol 2003;74:479–85
  • Pasare C, Medzhitov R. Toll-like receptors: linking innate and adaptive immunity. Microbes Infect 2004;6:1382–7
  • Hargreaves DC, Medzhitov R. Innate sensors of microbial infection. J Clin Immunol 2005;25:503–10
  • Castellheim A, Brekke OL, Espevik T, et al. Innate immune responses to danger signals in systemic inflammatory response syndrome and sepsis. Scand J Immunol 2009;69:479–91
  • Beutler B. Innate immune sensing of microbial infection: the mechanism and the therapeutic challenge. Wien Med Wochenschr 2002;152:547–51
  • Beutler B. Science review: key inflammatory and stress pathways in critical illness - the central role of the Toll-like receptors. Crit Care 2003;7:39–46
  • Akira S, Takeda K, Kaisho T. Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2001;2:675–80
  • Cario E, Brown D, McKee M, et al. Commensal-associated molecular patterns induce selective toll-like receptor-trafficking from apical membrane to cytoplasmic compartments in polarized intestinal epithelium. Am J Pathol 2002;160:165–73
  • Baker BS, Ovigne JM, Powles AV, et al. Normal keratinocytes express Toll-like receptors (TLRs) 1, 2 and 5: modulation of TLR expression in chronic plaque psoriasis. Br J Dermatol 2003;148:670–9
  • Hertz CJ, Wu Q, Porter EM, et al. Activation of Toll-like receptor 2 on human tracheobronchial epithelial cells induces the antimicrobial peptide human beta defensin-2. J Immunol 2003;171:6820–6
  • Kim YM, Romero R, Chaiworapongsa T, et al. Toll-like receptor-2 and -4 in the chorioamniotic membranes in spontaneous labor at term and in preterm parturition that are associated with chorioamnionitis. Am J Obstet Gynecol 2004;191:1346–55
  • Elovitz MA, Wang Z, Chien EK, et al. A new model for inflammation-induced preterm birth: the role of platelet-activating factor and Toll-like receptor-4. Am J Pathol 2003;163:2103–11
  • Dale M, Nicklin MJ. Interleukin-1 receptor cluster: gene organization of IL1R2, IL1R1, IL1RL2 (IL-1Rrp2), IL1RL1 (T1/ST2), and IL18R1 (IL-1Rrp) on human chromosome 2q. Genomics 1999;57:177–9
  • Tominaga S, Inazawa J, Tsuji S. Assignment of the human ST2 gene to chromosome 2 at q11.2. Hum Genet 1996;97:561–3
  • Bergers G, Reikerstorfer A, Braselmann S, et al. Alternative promoter usage of the Fos-responsive gene Fit-1 generates mRNA isoforms coding for either secreted or membrane-bound proteins related to the IL-1 receptor. EMBO J 1994;13:1176–88
  • Xu D, Chan WL, Leung BP, et al. Selective expression of a stable cell surface molecule on type 2 but not type 1 helper T cells. J Exp Med 1998;187:787–94
  • Lohning M, Stroehmann A, Coyle AJ, et al. T1/ST2 is preferentially expressed on murine Th2 cells, independent of interleukin 4, interleukin 5, and interleukin 10, and important for Th2 effector function. Proc Natl Acad Sci U S A 1998;95:6930–5
  • Kakkar R, Lee RT. The IL-33/ST2 pathway: therapeutic target and novel biomarker. Nat Rev Drug Discov 2008;7:827–40
  • Schmitz J, Owyang A, Oldham E, et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 2005;23:479–90
  • Coyle AJ, Lloyd C, Tian J, et al. Crucial role of the interleukin 1 receptor family member T1/ST2 in T helper cell type 2-mediated lung mucosal immune responses. J Exp Med 1999;190:895–902
  • Townsend MJ, Fallon PG, Matthews DJ, et al. T1/ST2-deficient mice demonstrate the importance of T1/ST2 in developing primary T helper cell type 2 responses. J Exp Med 2000;191:1069–76
  • Mildner M, Storka A, Lichtenauer M, et al. Primary sources and immunological prerequisites for sST2 secretion in humans. Cardiovasc Res 2010;87:769–77
  • Liu J, Buckley JM, Redmond HP, Wang JH. ST2 negatively regulates TLR2 signaling, but is not required for bacterial lipoprotein-induced tolerance. J Immunol 2010;184:5802–8
  • Buckley JM, Liu JH, Li CH, et al. Increased susceptibility of ST2-deficient mice to polymicrobial sepsis is associated with an impaired bactericidal function. J Immunol 2011;187:4293–9
  • Oshikawa K, Kuroiwa K, Tago K, et al. Elevated soluble ST2 protein levels in sera of patients with asthma with an acute exacerbation. Am J Respir Crit Care Med 2001;164:277–81
  • Oshikawa K, Yanagisawa K, Tominaga S, Sugiyama Y. Expression and function of the ST2 gene in a murine model of allergic airway inflammation. Clin Exp Allergy 2002;32:1520–6
  • Oshikawa K, Yanagisawa K, Tominaga S, Sugiyama Y. ST2 protein induced by inflammatory stimuli can modulate acute lung inflammation. Biochem Biophys Res Commun 2002;299:18–24
  • Hayakawa H, Hayakawa M, Kume A, Tominaga S. Soluble ST2 blocks interleukin-33 signaling in allergic airway inflammation. J Biol Chem 2007;282:26369–80
  • Kearley J, Buckland KF, Mathie SA, Lloyd CM. Resolution of allergic inflammation and airway hyperreactivity is dependent upon disruption of the T1/ST2-IL-33 pathway. Am J Respir Crit Care Med 2009;179:772–81
  • Kurokawa M, Matsukura S, Kawaguchi M, et al. Expression and effects of IL-33 and ST2 in allergic bronchial asthma: IL-33 induces eotaxin production in lung fibroblasts. Int Arch Allergy Immunol 2011;155:12–20
  • Tajima S, Oshikawa K, Tominaga S, Sugiyama Y. The increase in serum soluble ST2 protein upon acute exacerbation of idiopathic pulmonary fibrosis. Chest 2003;124:1206–14
  • Tajima S, Bando M, Ohno S, et al. ST2 gene induced by type 2 helper T cell (Th2) and proinflammatory cytokine stimuli may modulate lung injury and fibrosis. Exp Lung Res 2007;33:81–97
  • Hacker S, Lambers C, Pollreisz A, Hoetzenecker K, et al. Increased soluble serum markers caspase-cleaved cytokeratin-18, histones, and ST2 indicate apoptotic turnover and chronic immune response in COPD. J Clin Lab Anal 2009;23:372–9
  • Weinberg EO, Shimpo M, Hurwitz S, et al. Identification of serum soluble ST2 receptor as a novel heart failure biomarker. Circulation 2003;107:721–6
  • Sabatine MS, Morrow DA, Higgins LJ, et al. Complementary roles for biomarkers of biomechanical strain ST2 and N-terminal prohormone B-type natriuretic peptide in patients with ST-elevation myocardial infarction. Circulation 2008;117:1936–44
  • Granne I, Southcombe JH, Snider JV, et al. ST2 and IL-33 in pregnancy and pre-eclampsia. PLoS One 2011;6:e24463
  • Stampalija T, Chaiworapongsa T, Chaemsaithong P, et al. Maternal Plasma Concentrations of sST2 and Angiogenic/Anti-angiogenic Factors in Preeclampsia. J Matern Fetal Neonatal Med 2013; May 20 [e-pub ahead of print]
  • Brunner M, Krenn C, Roth G, et al. Increased levels of soluble ST2 protein and IgG1 production in patients with sepsis and trauma. Intensive Care Med 2004;30:1468–73
  • Hoogerwerf JJ, Tanck MW, van Zoelen MA, et al. Soluble ST2 plasma concentrations predict mortality in severe sepsis. Intensive Care Med 2010;36:630–7
  • Stampalija T Romero R, Korzeniewski S, et al. Soluble ST2 in the fetal inflammatory response syndrome: in-vivo evidence of activation of the anti-inflammatory limb of immune response. J Matern Fetal Neonatal Med 2013: In press
  • Guinn DA, Goldenberg RL, Hauth JC, et al. Risk factors for the development of preterm premature rupture of the membranes after arrest of preterm labor. Am J Obstet Gynecol 1995;173:1310–15
  • Romero R, Nores J, Mazor M, et al. Microbial invasion of the amniotic cavity during term labor. Prevalence and clinical significance. J Reprod Med 1993;38:543–8
  • Yoon BH, Romero R, Moon JB, et al. Clinical significance of intra-amniotic inflammation in patients with preterm labor and intact membranes. Am J Obstet Gynecol 2001;185:1130–6
  • Romero R, Jimenez C, Lohda AK, et al. Amniotic fluid glucose concentration: a rapid and simple method for the detection of intraamniotic infection in preterm labor. Am J Obstet Gynecol 1990;163:968–74
  • Romero R, Emamian M, Quintero R, et al. The value and limitations of the Gram stain examination in the diagnosis of intraamniotic infection. Am J Obstet Gynecol 1988;159:114–19
  • Iwahana H, Yanagisawa K, Ito-Kosaka A, et al. Different promoter usage and multiple transcription initiation sites of the interleukin-1 receptor-related human ST2 gene in UT-7 and TM12 cells. Eur J Biochem 1999;264:397–406
  • Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med 2003;348:138–50
  • Sweet MJ, Leung BP, Kang D, et al. A novel pathway regulating lipopolysaccharide-induced shock by ST2/T1 via inhibition of Toll-like receptor 4 expression. J Immunol 2001;166:6633–9
  • Leung BP, Xu D, Culshaw S, et al. A novel therapy of murine collagen-induced arthritis with soluble T1/ST2. J Immunol 2004;173:145–50
  • Mitchell MD, Simpson KL, Keelan JA. Paradoxical proinflammatory actions of interleukin-10 in human amnion: potential roles in term and preterm labour. J Clin Endocrinol Metab 2004;89:4149–52
  • Medzhitov R, Schneider DS, Soares MP. Disease tolerance as a defense strategy. Science 2012;335:936–41
  • Kim MJ, Romero R, Gervasi MT, et al. Widespread microbial invasion of the chorioamniotic membranes is a consequence and not a cause of intra-amniotic infection. Lab Invest 2009;89:924–36
  • Seong HS, Lee SE, Kang JH, et al. The frequency of microbial invasion of the amniotic cavity and histologic chorioamnionitis in women at term with intact membranes in the presence or absence of labor. Am J Obstet Gynecol 2008;199:375 e371–5
  • Kusanovic JP, Espinoza J, Romero R, et al. Clinical significance of the presence of amniotic fluid ‘sludge’ in asymptomatic patients at high risk for spontaneous preterm delivery. Ultrasound Obstet Gynecol 2007;30:706–14
  • Lee SE, Romero R, Kim CJ, et al. Funisitis in term pregnancy is associated with microbial invasion of the amniotic cavity and intra-amniotic inflammation. J Matern Fetal Neonatal Med 2006;19:693–7
  • Yoon BH, Romero R, Moon J, et al. Differences in the fetal interleukin-6 response to microbial invasion of the amniotic cavity between term and preterm gestation. J Matern Fetal Neonatal Med 2003;13:32–8
  • Romero R, Espinoza J, Kusanovic JP, et al. The preterm parturition syndrome. BJOG 2006;113:17–42
  • Kim CJ, Romero R, Kusanovic JP, et al. The frequency, clinical significance, and pathological features of chronic chorioamnionitis: a lesion associated with spontaneous preterm birth. Mod Pathol 2010;23:1000–11
  • Goldenberg RL, Hauth JC, Andrews WW. Intrauterine infection and preterm delivery. N Engl J Med 2000;342:1500–7
  • Topping V, Romero R, Than NG, et al. Interleukin-33 in the Human Placenta. J Matern Fetal Neonatal Med 2013;26:327–38

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.