Further observations on the fetal inflammatory response syndrome: A potential homeostatic role for the soluble receptors of tumor necrosis factor alpha

OBJECTIVE: The fetal inflammatory response syndrome is a subclinical condit ion frequently present in preterm labor and preterm premature rupture of th e membranes and is associated with increased perinatal morbidity and mortal ity. Tumor necrosis factor a is a mediator of septic shock and death, and i t exerts its biologic effects by interacting with 2 receptors, TNF-R1 and T NF-R2. Soluble tumor necrosis factor receptors can buffer the biologic acti vity and protect against the deleterious effects of tumor necrosis factor a lpha. The purpose of this study was to determine the behavior of soluble tu mor necrosis factor receptors in fetuses with and without fetal inflammator y response syndrome. STUDY DESIGN: Fetal blood sampling was performed in patients with preterm l abor (n = 95) and preterm premature rupture of the membranes (n = 39). Cont rol samples were obtained from fetuses who were undergoing blood sampling f or clinical indications and had normal outcomes (n = 21). Fetal inflammator y response syndrome was defined as a fetal plasma interleukin 6 concentrati on >11 pg/mL. Concentrations of interleukin 6 and TNF-R1 and TNF-R2 were de termined by use of sensitive and specific immunoassays. Analysis of covaria nce was used for statistical analysis. RESULTS: (1)TNF-R1 and TNF-R2 were detectable in all samples, and their con centrations decreased with advancing gestational age (r = -0.8 and r = -0.7 ; P < .0001 and P < .001, respectively). (2) The mean fetal plasma concentr ations of TNF-RI and TNF-R2 were significantly higher in fetuses with fetal inflammatory response syndrome than in those without the syndrome after ad justment for gestational age and fetal membrane status (TNF-R1: no fetal in flammatory response syndrome, mean +/- SE. 3473.7 +/- 128.8 pg/mL; vs fetal inflammatory response syndrome, mean +/- SE, 4079.9 +/- 190.7 pg/mL; P < . 005;TNF-R2: no fetal inflammatory response syndrome, mean +/- SE, 6033.2 +/ - 235.4 pg/mL; vs fetal inflammatory response syndrome, mean +/- SE, 7783.1 +/- 342.8 pg/mL; P < .0001). (3) Fetuses of patients who delivered within 72 hours of cordocentesis had significantly higher concentrations of TNF-R1 and TNF-R2 receptors than those with longer latency periods (P < .05 for e ach). CONCLUSION: The fetal inflammatory response syndrome is associated with inc reased availability of the soluble receptors of tumor necrosis factor <alph a> in fetal plasma. These factors may attenuate the deleterious effects of tumor necrosis factor alpha.