Intraperitoneal infusion of proinflammatory cytokines does not cause activation of the rat uterus during late gestation.
Increased concentrations of IL-1beta and TNF-alpha 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)F(2alpha) (FP), PGH(2) synthase isoform 2 (PGHS2), the gap junction protein connexin-43 (Cx-43), and the inducible isoform of nitric oxide synthase (iNOS). To determine whether IL-1beta or TNF-alpha was part of the causal mechanism for increased uterine contractions, we placed osmotic pumps infusing IL-1beta or TNF-alpha 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-1beta and TNF-alpha were increased significantly. By day 21, the control animals had significant increases (P < or = 0.05) in mRNA for OT, FP, PGHS2, and Cx-43, a decrease (P < or = 0.05) in iNOS, and an increase (P < or = 0.05) in uterine sensitivity and responsiveness to OT. Infusion of IL-1beta or TNF-alpha had no effect on uterine contractility or on expression of the activation-associated genes. We conclude that intraperitoneal infusion of IL-1beta or TNF-alpha 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.
Mitchell
Bryan F
BF
Perinatal Research Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2S2. brymitch@ualberta.ca
Zielnik
Barbara
B
Wong
Susan
S
Roberts
Carla D
CD
Mitchell
Jana M
JM
D000818:Animals; D016207:Cytokines / Q000097:blood; D005260:Female; D007262:Infusions, Intravenous; D007375:Interleukin-1 / Q000008:administration & dosage / Q000097:blood*; D036801:Parturition / Q000502:physiology*; D011247:Pregnancy / Q000502:physiology*; D011270:Pregnancy, Animal / Q000097:blood / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000032:analysis* / Q000378:metabolism*; D014590:Uterine Contraction / Q000502:physiology*
D016207:Cytokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha