Pregnancy

Effects of endotoxin and macrophage-related cytokines on the contractile activity of the gravid murine uterus

Abstract

Trafficking and activity by immune cells are implicated in the parturition process but little is known about the role of macrophages in control of uterine contractility at term. The present study tested the hypothesis that endotoxin (lipopolysaccharide, LPS) enhances uterine contractile activity through a mechanism that involves activation of resident macrophages. Various uterotonins and anti-inflammatory mediators were added to a standard muscle bath preparation that contained strips of uterus from day 15 pregnant C3H/HeN mice. Spontaneous and agonist-induced contractile activity was enhanced following LPS treatment. LPS increased amplitude but not frequency of contractions. Addition of anti-inflammatory cytokines, IL-10 or TGF, to suppress macrophage activation did not block LPS-induced increases in contractility. By contrast, indomethacin given to block prostaglandin production, suppressed the LPS-induced increase in amplitude of contractions. Findings suggest that an inflammatory response, possibly mediated by activation of macrophage and prostaglandins, participates in the regulation of amplitude, as opposed to frequency, of contractile activity by the murine uterus before onset of parturition.