Amnion cell biosynthesis of interleukin‐8: Regulation by inflammatory cytokines

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Abstract
The cellular constituents of the placenta are important participants in the recruitment and trafficking of inflammatory cells within the placenta. In infectioninduced labor, gestational tissues synthesize and release a variety of inflammatory cytokines whose effects include increased prostaglandin biosynthesis and the initiation of uterine contractions. Interleukin-8 (IL-8), a potent neutrophil chemoattractant, has been recently described as being elevated in the amniotic fluid of mothers with chorioamnionitis. We investigated the biosynthesis of IL-8 by human amnion cells and its regulation by other inflammatory cytokines. Cultured amnion cells obtained from normal term placentae were found to produce IL-8 in response to pathophysiologic concentrations of interleukin 1β (IL-1β) and tumor necrosis factor alpha (TNF-α). Treatment of amnion cells stimulated by IL-1β with cycloheximide resulted in increased IL-8 production, while incubation of IL-1β treated amnion cells with actinomycin D resulted in a concentration-dependent decrease in detectable amounts of IL-8. Northern blot analysis of cultured amnion cells stimulated with IL-1β demonstrated a rapid increase in IL-8 mRNA which peaked at 2–4 hr. These in vitro result suggest inflammation of gestational tissues in vivo may result in locally produced IL-8 and, in association with other inflammatory mediators, may be important in the pathophysiology of infection-induced labor.