TNF, IL-1, IL-6, IL-8 and soluble TNF receptors in relation to chorioamnionitis and premature labor.

Inflammatory cytokines seem to play a key role in mechanisms initiating labor. Since cytokine levels are higher in preterm than in term labor, it has been hypothesized that labor-inducing effects of cytokines are inhibited by an upregulated production of cytokine antagonists, such as soluble cytokine receptors, at early stages of gestation. In this study, TNF, IL-1, IL-6, IL-8 and soluble TNF receptors (sTNFRs) were measured in amniotic fluid samples from a) 39 women in premature labor, b) 25 women who where not in labor but delivered prematurely, and c) 33 women in term labor. Fifty-four of the placentas from premature deliveries were evaluated for presence of histological chorioamnionitis. Chorioamnionitis was associated with increased levels of TNF, IL-1 and IL-6, whereas elevated IL-1, IL-6 and IL-8 concentrations were found in premature parturition with no signs of infection. Concentrations of sTNFR were lower in preterm than in term deliveries. The present study confirms the participation of inflammatory cytokines in parturition. Multivariate analysis suggests a dominant, role of IL-1 in the presence of chorioamnionitis, whereas IL-6 seems to be more important during idiopathic premature labor. TNFR data do not support the hypothesis that production of cytokine antagonists is upregulated prematurely to prevent partirution.

Cytokine levels in amniotic fluid and inflammatory changes in the placenta from normal deliveries at term.

Cytokine levels in amniotic fluid have been shown to increase towards term in normal pregnancies, and may play a regulatory role in parturition by stimulating the local production of prostaglandins. The work reported in the present paper was conducted in order to test the hypothesis that the increased cytokine levels may be induced by a subclinical inflammatory reaction in intrauterine tissues. The concentrations of tumor necrosis factor (TNF), interleukin 1 (IL-1), interleukin 2 (IL-2) and interleukin 6 (IL-6) were determined in samples of amniotic fluid from 38 women in delivery at term, after a clinically normal pregnancy. In 33 of the cases, tissue material was available for histological examination. In these, the extent of inflammatory cell infiltration was assessed in the fetal membranes, placenta and umbilical cord. A close interrelation was observed between the levels of the mediators typically released during inflammatory processes (TNF, IL-1, IL-6). Frank chorioamnionitis was not found in any of the histological specimens, although most placentae showed varying degrees of granulocyte infiltration in the fibrin layer under the chorion, sometimes also in the chorionic membrane. The degree of such leukocytic infiltration correlated positively with the levels of TNF, IL-1 and IL-6. These findings lend support to the hypothesis that a low-level inflammatory process may be a normal occurrence in the term placenta, and that this process may induce the production of cytokines, which, in turn, may play a role in the regulation of parturition. Such inflammation could be due to exposure of the fetal membranes to microbial material from the vagina, as the cervix dilates towards term.

[Normal labor. Is it induced as a result of subtle intrauterine inflammatory reactions?]. / Den normale fødsel. Settes den i gang som resultat av subtile inflammatoriske reaksjoner intrauterint?

The present study was conducted in order to test the hypothesis the elevated cytokine levels in amniotic fluid from normal deliveries may be generated by a subclinical inflammatory response in intrauterine tissue. Specimens were collected from 38 women with normal deliveries. The levels of tumour necrosis factor, IL1 and IL6 in amniotic fluid samples correlated with the extent of inflammatory cell infiltration in specimens of the foetal membranes, placenta and umbilical cord. Tumour necrosis factor, IL1 and IL6 are generally produced as part of the inflammatory reaction and stimulate synthesis of prostaglandin. Thus a subclinical, intrauterine inflammatory response may play a role in initiation of normal parturition at term.

Soluble receptors for tumor necrosis factor: occurrence in association with normal delivery at term.

OBJECTIVE: To compare levels of tumor necrosis factor (TNF) and interleukin 1 (IL-1) and 6 (IL-6) with levels of the soluble receptors for TNF in maternal and neonatal urine and amniotic fluid (AF). METHODS: Levels of soluble TNF receptors (p55, p75) in AF and urine from 21 women and their newborns were measured by immunoassay. The amniotic concentrations of IL-1 and IL-6 were assessed by biologic assays, whereas an immunoassay was used to measure TNF levels. The comparison between receptor concentrations in different compartments was performed by one-way analysis of variance, and Student t test was used to compare pairs of groups. Correlation studies were performed when indicated. RESULTS: A high correlation was observed between the concentrations of p55 and p75 in all compartments. The concentration of p55 in AF was significantly higher than that in both maternal and neonatal urine, but the correlation between TNF receptor concentrations in the AF samples and the concomitant levels of cytokines was not statistically significant. CONCLUSION: The high concentration of receptors in the AF compared to those of other biologic compartments suggests that the pregnancy-associated increased receptor shedding takes place in intrauterine tissues. Physiologic levels of cytokines, such as those accompanying normal delivery at term, did not seem to influence the soluble TNF receptor release.