Interleukin-1beta (IL-1beta) is not detected in the amniotic fluid of normal human pregnancies before the initiation of parturition, but during labor, both at term and preterm, this cytokine is present in the amniotic fluid of 25-40% of pregnancies. A critical question, however, is whether this finding is indicative of a role for IL-1beta (directly or indirectly) in the initiation of parturition or is the result of IL-1beta formation and entry into amniotic fluid as a natural sequela of normal labor. The forebag of the amniotic sac is formed during labor in response to cervical dilatation, and on the decidual surface, the tissues of this structure become exposed and bathed by vaginal fluids as the cervix opens. Microorganisms and bacterial toxins are present in vaginal fluid before labor begins; these agents should act upon the exposed tissues of the forebag to cause inflammation and evoke an inflammatory response. This study was conducted to examine the likelihood that the inflammatory mediators found in amniotic fluid in increased amounts at parturition are produced in forebag tissues after the onset of labor because of obliged inflammation in these tissues. Vaginal/cervical fluids were collected by lavage from nonpregnant women and from pregnant women at term before and during labor. The amount of immunoreactive IL-1beta in vaginal/cervical fluids of pregnant women during labor (mean +/- SEM, 91.5 +/- 16.9 ng; n = 17) was significantly greater (P < 0.001) than that in fluids collected before labor (7.8 +/- 3 ng; n = 14). The in vivo rate of IL-1beta secretion directly from the decidua lining the forebag during labor was brisk (1.71 +/- 0.88 ng/cm2.min; n = 4), consistent with previous observations of higher levels of pro-IL-1beta mRNA in decidual tissues adherent to the forebag compared with those in decidua adherent to chorion laeve of the upper compartment of the amnionic sac. The vaginal fluid content of prostaglandins (PGs) during labor [PGE2, 82.1 +/- 16.4 ng; PGF2alpha, 141.5 +/- 30.5 ng; PGFM, 35.2 +/- 5.8 ng (mean +/- SEM; n = 13)] was significantly greater for PGE2 and PGF2alpha (P < 0.05 and 0.004, respectively) than that before labor (PGE2, 42.6 +/- 9.4 ng; PGF2alpha, 35.3 +/- 8.5 ng; PGFM, 21.7 +/- 4.6 ng; n = 12). In addition, there was a significant increase in the ratio of PGF2alpha to PGE2 (P < 0.03) in vaginal fluids during labor. The amounts of IL-1beta and PGs in vaginal fluids of nonpregnant women were similar to those in pregnant women before the onset of labor. We conclude that the increases in IL-1beta and PGs in vaginal/cervical fluids at parturition arise by direct secretion from tissues (principally decidua) that line the forebag. In pregnancies with intact membranes, this tissue site of inflammation is the likely source, directly or indirectly, of the mediators of the inflammatory response that enter amniotic fluid during labor; therefore, the accumulation of these agents in amniotic fluid is a sequela of labor and not indicative of a role for IL-1beta or PGs in the initiation of parturition.
