243. Interleukin-6 is an essential regulator of parturition and perinatal viability in mice

Abstract

IL-6 is an immune-regulatory cytokine which has functional overlap with LIF and IL-11 due to shared use of the gp130 receptor. IL-6 is synthesised abundantly in the uterus throughout pregnancy and at the time of parturition. Previously we have shown that mice with a null mutation in the Il6 gene (Il6−/−) have elevated rates of fetal resorption (45% v. 14% in WT controls) and a high incidence of postnatal death. Additionally, timing of birth is delayed ~24 h in Il6−/− mice (1), in association with altered uterine expression of several parturition-associated genes including PGHS-2, PTGFR and CX-43, and delayed progesterone decline (2). To investigate the effect of exogenous IL-6 replacement on perinatal parameters, Il6−/− and WT females were mated with males of the same genotype and on day 11.5 pc were surgically implanted subcutaneously with Alzet micro-osmotic pumps (7 day) containing 1 μg rhIL-6 (R&D Systems), or PBS+0.1% BSA carrier alone (n = 12 females per group). The mean time of parturition was advanced after rhIL-6 replacement in Il6−/− females from day 20.3 pc to day 19.6 pc (P < 0.05), but was unchanged in WT mice (day 19.5). As expected, the number of viable pups delivered by Il6−/− mice was less than in WT mice, but was unchanged in either group by IL-6 replacement. However rhIL6 replacement in Il6−/− mice substantially increased the proportion of neonates that survived to weaning (from 60% to 98%, P < 0.05), with no effect on postnatal survival in WT mice (76% v. 88%). Together these data provide further evidence supporting a central role for IL-6 in the events of parturition and postnatal survival, and indicate that exogenous IL-6 replacement in IL-6 deficient mice can improve perinatal outcomes.

(1) Robertson et al. ASRB 31 Abstract 97, 2000

(2) Robertson et al. SGI Abstract 729, 2008