Localization and regulation of IL-1 alpha in rat myometrium during late pregnancy and the postpartum period

Interleukin-1 (IL-1) has been implicated as a participant in preterm labor that is induced by bacterial infection. Previously, we showed that serotoni n-induced production of IL-1 alpha by myometrial smooth muscle cells in vit ro is also essential for the synthesis of interstitial collagenase. It is t herefore likely that IL-1 alpha production in uterine tissues has implicati ons for both the normal physiology of involution and for the pathophysiolog ical mechanisms of preterm labor. The objective of this study was to charac terize the serotonin-induced production of IL-1 alpha by myometrial culture s in vitro and to assess the production of IL-1 alpha and its relationship to collagenase production in vivo during pregnancy and the postpartum perio d. Immunohistochemistry demonstrated IL-1 alpha protein in the nuclei and c ytoplasm of serotonin-treated myometrial cells. IL-1 alpha levels were decr eased by treatment with progesterone or IL-1-receptor antagonist but were u naffected by lipopolysaccharide. Western analysis of myometrium from pregna nt rats showed low levels of IL-1 alpha during midpregnancy with increased concentrations at days 21 and 22 and postpartum. IL-1 alpha mRNA levels als o increased from days 15 to 22. Levels of mRNA for IL-1 beta also increased , although to a lesser degree than IL-1 alpha. Both mRNAs decreased postpar tum. Conversely, mRNA for interstitial collagenase was barely detectable at term but increased postpartum. Together, these data show that serotonin st imulates IL-1 alpha production in vitro and indicate that normal myometrium from pregnant rats is an identifiable source of IL-1 during late pregnancy . The findings are consistent with the possibility that myometrial IL-1 alp ha participates in normal labor as well as the postpartum production of int erstitial collagenase.