ENDOTOXIN STIMULATES INTERLEUKIN-6 PRODUCTION IN INTESTINAL EPITHELIAL-CELLS A SYNERGISTIC EFFECT WITH PROSTAGLANDIN E(2)

Objective: To test the hypothesis that endotoxin stimulates the releas e of interleukin-6 (IL-6) from intestinal epithelial cells and that th is effect of endotoxin is regulated by prostaglandin E(2) (PGE(2)). De sign: A rat intestinal crypt cell line, IEC-6, was cultured in the pre sence of lipopolysaccharide (LPS), 0.1 to 1.0 mu g/mL, and/or PGE(2), 1 mu mol/L. In other experiments, indomethacin, 20 mu mol/L, was added to LPS-treated cells to block the effects of prostaglandins. Control wells contained medium alone. Levels of IL-6 were determined by the B9 murine hybridoma bioassay. Polymerase chain reaction was performed on RNA from control and LPS-treated cells to examine IL-6 message. Resul ts: Lipopolysaccharide and PGE(2) induced IL-6 release from IEC-6 cell s in a dose- and time-dependent fashion, and the substances interacted synergistically. Addition of indomethacin blunted the effect of endot oxin on IL-6 production, consistent with a stimulatory role of PGE(2). Polymerase chain reaction demonstrated increased IL-6 messenger RNA i n endotoxin-treated cells. Conclusions: Endotoxin and PGE(2) stimulate IL-6 production in IEC-6 cells and interact synergistically. The endo toxin-stimulated IL-6 release may be regulated at the transcriptional level.