Effect of IL-1β and IL-6 on oxytocin secretion in human uterine smooth muscle cells

Problem: Infection-mediated preterm labor results in the production of inflammatory cytokines, including interleukin-1β (IL-1β) and interleukin-6 (IL-6). Oxytocin (OT) plays a key role in the process of labor. This study investigates the effect of IL-1β and IL-6 on intra-and extracellular OT in human smooth muscle cells and evaluates IL-1β induced changes in IL-6 production. Method of study: Primary cultures of human myometrium, obtained from term pregnant women (n = 7) were incubated with either IL-1β or IL-6 for 0-24 hr. Intra- and extracellular OT peptide concentrations were measured by radioimmunoassay and IL-6 mRNA and protein were evaluated by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Results: Both, IL-1β and IL-6 led to an increase in OT secretion, which was accompanied by a reduction of the intracellular OT peptide pool. IL-1β significantly induced IL-6 mRNA expression and protein secretion, which did not further enhance IL-1β induced OT secretion. Conclusions: The induction of OT secretion by proinflammatory cytokines in human myometrium in vitro, supports the concept of a thus regulated infection-triggered preterm labor process in vivo.