The participation of interleukin-6 (IL-6) in the pathophysiology of normal and abnormal human parturition was evaluated by determining IL-6 concentrations in amniotic fluid (AF). Biologically active IL-6 was determined (in U/ml) using the B9 hybridoma growth factor assay, while the concentrations of immunoreactive IL-6 species (in pg/ml) were assessed using a monoclonal antibody (moAb)-based ELISA. Two hundred and twenty-seven AF samples from women in normal labor and from those presenting with a clinical diagnosis of premature rupture of membranes (PROM) were assayed. In selected instances, IL-6 levels were evaluated simultaneously in AF and in maternal and fetal plasma. Women with a normal pregnancy had low titers of biologically active IL-6 in AF both at midtrimester (group 1, n = 27; median IL-6 concentration = 16 U/ml) and at term (group 2, n = 33; median = 15 U/ml). There was an increase in the IL-6 bioactivity in AF from women in normal labor at term (group 3, n = 40; median = 74 U/ml; p < 0.001). In order to distinguish between the relative contributions of parturition per se and of intrauterine infection to the elevation of biologically active IL-6 levels in AF, IL-6 titers were compared in four different groups of women with PROM. Median AF IL-6 titers were 67 U/ml in women with microbial culture-negative AF who were not in active labor at the time of admission (group 4a, n = 17); 109 U/ml in those with culture-negative AF who were in active labor (group 4b, n = 25); 336 U/ml in those with culture-positive AF who were not in labor (group 4c, n = 21) and 4,330 U/ml in women with culture-positive AF who were in labor (group 4d, n = 33). The IL-6 ELISA provided data consistent with the B9 bioassay results. The median concentrations of AF IL-6 in women at midtrimester (n = 16) and in those at term who were not in labor (n = 15) were both 200 pg/ml; those in women with PROM were 800, 1,000, 2,320, and 18,800 pg/ml in groups 4a (n = 12), 4b (n = 23), 4c (n = 14), and 4d (n = 31), respectively. Taken together, these data indicate that: (1) PROM per se may be associated with a modest elevation of AF IL-6 titers; (2) in the absence of infection, preterm parturition is not associated with a further elevation of AF IL-6; and most strikingly, (3) intraamniotic microbial infection is associated with marked elevations of AF IL-6 that are particularly high when associated with active parturition (p < 0.001). A marked elevation in the AF IL-6 level was sometimes, but not always, accompanied by an elevation of the IL-6 level in the fetal circulation and vice versa, suggesting that separate pathologic events trigger IL-6 accumulation in these two intrauterine compartments. At best, only trace levels of IL-6 biological activity and immunoreactivity were observed in the maternal circulation, even in women with markedly elevated amniotic fluid and/or fetal plasma IL-6. The present data clearly implicate IL-6 in the physiology of normal human parturition and also point to a strong association between markedly elevated AF or fetal plasma IL-6 levels and abnormal labor that accompanies intrauterine infection. © 1991.
