The production of interleukin-1β from human fetal membranes is not obligatory for increased prostaglandin output.

Bacterial endotoxin increased the expression of mRNA (maximal after 4 hr) for interleukin-1β (IL-1β) and the release of mature protein from intact human fetal membranes. In contrast, the change in expression of mRNA for type 2 cyclo-oxygenase (COX-2) was biphasic, with peaks after 0·5–1 hr and after 8 hr of culture. An antibody to IL-1β was without effect after 4 hr of culture, inhibited endotoxin-stimulated prostaglandin E2 (PGE2) production after 8 hr of culture, and caused a parallel decrease in the expression of mRNA for COX-2. We conclude that endotoxin induced the expression of COX-2 through IL-1β-independent and IL-1β-dependent mechanisms, and these differences are time dependent. Corticotrophin-releasing hormone (CRH) or platelet-activating factor (PAF) also increased the expression of mRNA for IL-1β and the release of IL-1β from some, but not all, fetal membranes. The antibody to IL-1β did not affect CRH-stimulated or PAF-stimulated PGE2 production or COX-2 expression. We conclude that CRH and PAF can induce the expression of IL-1β, but this is not obligatory for increased PGE2 release, and the effect of these stimuli on COX-2 expression is a direct, IL-1β-independent effect. [ABSTRACT FROM AUTHOR]