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

ABSTRACT

Human term myometrium is poorly characterized as a source of proinflammatory mediators involved in parturition. We have investigated the basal expression of cytokines in myometrium, as well as the effects of CRH and lipopolysaccharide (LPS) on cytokine release. Explants from term myometrium were challenged with CRH or LPS (1 microg/mL each) in short-term tissue culture. Interleukin (IL)-1beta++, IL-6, IL-8, and tumor necrosis factor (TNF)alpha concentrations in the medium were quantified 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 investigated by RT-PCR. IL-1beta+ and IL-6 messenger RNA were present in preterm and term myometrium before and during labor, whereas IL-8 and TNFalpha 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 proinflammatory cytokines and is involved in the inflammation-like reactions mediating the birth process. Cytokine release in term myometrium seems not to be under control of CRH.