Maternal IL-10 and IL-6 are elevated in response to localized intrauterine inflammation

Abstract

INTRAUTERINE INFLAMMATION MICHAL ELOVITZ, CONJEEVARAM MRINALINI, University of Pennsylvania, Philadelphia, Pennsylvania, University of Pennsylvania, Obstetrics and Gynecology, Philadelphia, Pennsylvania OBJECTIVE: Preterm birth is associated with a pro-inflammatory response in maternal tissues. Using a mouse model of localized intrauterine inflammation, we have demonstrated that, just prior to parturition, there is a potent TH1/TH2 response in the uterus and cervix. These studies were performed to elucidate which of these cytokines may play a primary role in activating an inflammatory response in the uterus and whether cytokine levels in the mother could predict the presence of a localized inflammatory state. STUDY DESIGN: On day 15 of gestation, CD-1 mice were randomized to intrauterine LPS or saline. At 1, 3, and 6 hours after intrauterine infusion, maternal serum, uterine and cervical tissues were collected. Real-time PCR was performed to determine message expression of IL-1b, TNF-a, IL-6, L-10, and IL-13 in the uterus and cervix. ELISAs were performed to correlate uterine mRNA and protein expression as well as determine cytokine levels in maternal serum. Statistical analysis using ANOVA and pairwise comparison was performed. RESULTS: TH1 and TH2 cytokine mRNA expression was significantly increased in the uterus and cervix rapidly after intrauterine infusion of LPS. Increased protein expression of IL-1, TNF, and IL-10 in the uterus was evident at 3 hrs. TNF and IL-1b levels in maternal serumwere not significantly elevated. In contrast, 3 hrs after intrauterine LPS, IL-10 and IL-6 were increased 18 and 6-fold respectively over controls. By 6 hrs, systemic IL-10 levels were still significantly elevated from controls but on a decreased compared to the 3 hr levels while IL-6 levels continued to increase and were O100-fold elevated compared to controls. CONCLUSION: Despite a potent proinflammatory response in the uterus and cervix in response to localized intrauterine inflammation, systemic levels of IL-1b and TNF-a are not reliable predictors of this inflammatory state. In contrast, elevated maternal IL-10 levels may be an early indicator of intrauterine inflammation and serial systemic IL-6 levels may predict localized inflammatory response in the uterus.