Intraperitoneal infusion of proinflammatory cytokines does not cause activation of the rat uterus during late gestation

Abstract

Increased concentrations of IL-1β and TNF-α have been associated with parturition. However, the role of these cytokines is unknown. Before parturition, the uterus undergoes a process of activation, during which there are significant changes in expression of genes associated with increased uterine contractility, including the receptors for oxytocin (OT) and prostaglandin (PG)F2α(FP), PGH2synthase isoform 2 (PGHS2), the gap junction protein connexin-43 (Cx-43), and the inducible isoform of nitric oxide synthase (iNOS). To determine whether IL-1β or TNF-α was part of the causal mechanism for increased uterine contractions, we placed osmotic pumps infusing IL-1β or TNF-α into the peritoneal cavity of late pregnant rats (gestation day 19) and measured the effects on uterine contractility and on the uterine concentrations of mRNA for the contraction-associated genes 24 h later. Maternal serum concentrations of IL-1β and TNF-α were increased significantly. By day 21, the control animals had significant increases ( P ≤ 0.05) in mRNA for OT, FP, PGHS2, and Cx-43, a decrease ( P ≤ 0.05) in iNOS, and an increase (P ≤ 0.05) in uterine sensitivity and responsiveness to OT. Infusion of IL-1β or TNF-α had no effect on uterine contractility or on expression of the activation-associated genes. We conclude that intraperitoneal infusion of IL-1β or TNF-α resulting in significantly increased maternal serum cytokine levels does not cause uterine activation. The role of proinflammatory cytokines in the mechanism of parturition remains unclear.