Formation of proinflammatory cytokines in human term myometrium is stimulated by lipopolysaccharide but not by corticotropin-releasing hormone

Human term myometrium is poorly characterized as a source of proinflammator y mediators involved in parturition. We have investigated the basal express ion of cytokines in myometrium, as well as the effects of CRH and lipopolys accharide (LPS) on cytokine release. Explants from term myometrium were challenged with CRH or LPS (1 mug/mL eac h) in short-term tissue culture. Interleukin (IL)-1 beta, IL-6, IL-8, and t umor necrosis factor (TNF)alpha concentrations in the medium were quantifie d by enzyme immunoassay. The major cytokines released after 24 h were IL-6 and IL-8. All cytokines investigated were stimulated significantly by LPS ( P < 0.05) but not by CRH. Messenger RNA levels of these cytokines were inve stigated by RT-PCR. IL-1<beta> and IL-6 messenger RNA were present in prete rm and term myometrium before and during labor, whereas IL-8 and TNF alpha were expressed only by myometrium in active labor. Furthermore, myometrial CRH receptors and macrophages were characterized immunohistochemically. We conclude that human term myometrium is a site of production of proinflam matory cytokines and is involved in the inflammation-like reactions mediati ng the birth process. Cytokine release in term myometrium seems not to be u nder control of CRH.