Regulation of lipopolysaccharide-induced tumor necrosis factor alpha production by endogenous prostaglandin E2 in rat resident and thioglycollate-elicited macrophages.

Prostaglandin E2 (PGE2) is generally accepted to be a negative feedback effector of tumor necrosis factor alpha (TNF alpha) production. However, we have observed that a cyclooxygenase inhibitor had different effects on TNF alpha production by resident and thioglycollate-elicited rat peritoneal macrophages. Indomethacin coordinately reduced PGE2 production and increased TNF alpha production in lipopolysaccharide (LPS)-stimulated resident macrophages, whereas indomethacin reduced PGE2 production without affecting TNF alpha production in thioglycollate-elicited macrophages. PGE2 production and arachidonate release were much less in thioglycollate-elicited macrophages than in resident macrophages. However, exogenously added PGE2 suppressed TNF alpha production to the same extent in the two macrophage populations. The addition of free arachidonic acid to cultures of LPS-stimulated, thioglycollate-elicited macrophages elevated PGE2 production and suppressed TNF alpha production in a manner similar to that observed with LPS-stimulated resident macrophages. These results indicate that the differential effects of indomethacin treatment on TNF alpha production observed between the two macrophage populations are not due to the differences in arachidonate contents, PGE2 productivities, nor to their capacities to respond to PGE2. Instead, the inability of indomethacin to increase TNF alpha production by thioglycollate-elicited versus resident macrophages appears to result from an inability to release arachidonate efficiently and a lower initial level of cyclooxygenase, in thioglycollate-elicited macrophages.