IMMUNOREACTIVE TUMOR-NECROSIS-FACTOR-ALPHA IS ELEVATED IN MATERNAL PLASMA BUT UNDETECTED IN AMNIOTIC-FLUID IN THE 2ND TRIMESTER

OBJECTIVE: We investigated the participation of the cellular arm of the immune system in adaptation to pregnancy by assessing plasma and amniotic fluid levels of the cytokine tumor necrosis factor-alpha. STUDY DESIGN: Fifty-five healthy pregnant women who underwent second-trimester genetic amniocentesis at a mean gestational age of 17.0+ +/- 1.4 weeks composed study group A. Blood was drawn from each patient before amniocentesis, and an aliquot of amniotic fluid was obtained for this study. Twenty-one healthy patients at a mean gestational age of 35.5 +/- 4.8 weeks composed study group B, and blood was obtained from each patient at an outpatient prenatal visit. Twenty-two healthy, nonpregnant women of reproductive age composed the control group (C). All specimens were stored at -70 degrees C and collectively assayed for tumor necrosis factor-alpha by a specific enzyme-linked immunoassay. RESULTS: All patients in group A had a normal karyotype and all patients in groups A and B had uneventful pregnancies. Tumor necrosis factor-alpha was detected in the plasma of 43 of 55 (78.2%) patients in group A compared with 7 of 21 (33.3%) patients in group B (p < 0.001); tumor necrosis factor-alpha was not detected in any of the 22 women in group C. The median plasma tumor necrosis factor-alpha level for group A was 135 pg/ml (range 0 to 625 pg/ml) compared with 0 pg/ml (range 0 to 110 pg/ml) in group B (p < 0.001). Tumor necrosis factor-alpha was not detected in any of the amniotic fluid specimens studied. CONCLUSIONS: Levels of tumor necrosis factor-alpha were elevated in the plasma but not detected in the amniotic fluid of normal pregnant patients in the second trimester. These findings suggest involvement of the cellular branch of the immune system and its products, the cytokines, in the normal adaptation of the mother to the fetal allograft, with a possible role in regulating trophoblast growth and invasion.