Regulation of murine macrophage Ia antigen expression by an immune interferon-like lymphokine: inhibitory effect of endotoxin.

The initiation of antigen-specific, T-dependent immune responses by macrophages requires their expression of Ia antigens. Ia antigen-deficient (Ia-) peritoneal exudate or P388D1 cell line macrophages, when incubated for 2 to 3 days with partially purified immune interferon (IFN-gamma), expressed Ia antigen, as detected by antibody-and-complement-mediated cytotoxicity. This paper reports that bacterial endotoxin (lipopolysaccharide, LPS) inhibited both IFN-gamma induction of macrophage Ia antigen expression and IFN maintenance of the Ia+ state in a dose-dependent manner. In the absence of IFN-gamma, LPS had no significant effect on macrophage Ia antigen expression. The inhibitory effects of LPS were abrogated by the addition of indomethacin into the culture medium. Further, 10(-10) to 10(-6) M exogenous prostaglandin E2 or 10(-6) to 10(-4) M exogenous dibutryl 3'5' cyclic adenosine monophosphate also inhibited IFN-gamma regulation of macrophage Ia antigen expression. The data suggest that LPS inhibits IFN-gamma regulation of macrophage Ia antigen expression by stimulating macrophage prostaglandin E2 production, and consequently enhancing intracellular cAMP levels. The data outline an inhibitory pathway involved in the regulation of macrophage Ia antigen expression, and may explain, in part, reported immunosuppressive effects of LPS.