THE EFFECT OF MONOPHOSPHORYL LIPID-A ON LIPOPOLYSACCHARIDE-INDUCED PROSTAGLANDIN E-2 RELEASE IN HUMAN CHORIODECIDUA

The aim of this study was to determine the effect of an inhibitor of b acterial endotoxin, monophosphoryl lipid A (MLA), on lipopolysaccharid e (LPS)-induced prostaglandin E-2 (PGE(2)) formation by human choriode cidua explants incubated in vitro. LPS induced the release of PGE(2) f rom explants in a time- and dose-dependent manner (P<0.05, n=5), thus establishing the efficacy of the experimental model. MLA at concentrat ions of 10 mu g/ml also increased PGE(2) release from explants when co mpared to vehicle controls (P<0.05, n=5). When used at a concentration that did not stimulate PGE(2) release (1 mu g/ml), MLA pretreatment, coincubation or a combination of these protocols did not significantly affect LPS-induced PGE(2) release. These data establish that MLA does not act by abrogating tissue LPS responsiveness. Under the conditions utilized in this study, MLA acts locally as a low potency 'LPS-like a gent'. The previously reported in vivo efficacy of systemically admini stered MLA map involve the partial depletion or down regulation of LPS response pathways and the subsequent development of LPS tolerance. (C ) 1997 W. B. Saunders Company Ltd.