title: Interferon-gamma reduces macrophage-suppressive activity by inhibiting prostaglandin E2 release and inducing interleukin 1 production.
abstract: Normal peritoneal M phi of C3H/HeN mice were able to suppress lymphocyte proliferation in a dose-dependent fashion when added to Con A-pulsed spleen cell cultures. However, M phi-suppressive activity could be partially or completely reduced by in vitro pre-exposure to nonimmune IFN-alpha or immune recombinant IFN-gamma. For both IFN-alpha and IFN-gamma, reduction of M phi suppression was marginal at 10(1) U/ml and became highly significant at 10(2) to 10(3)/ml. The ability of IFN-alpha and IFN-gamma to modulate M phi suppression appears to be related to distinct mechanisms. In fact, impairment of M phi suppression by IFN-alpha occurred in parallel to the decrease of M phi capacity to produce PGE2 and the oxygen intermediate O2-, two molecules responsible for M phi-suppressive activity. In contrast, M phi exposed to IFN-gamma showed only impairment of PGE2 production, whereas O2- release was not significantly affected. Furthermore, at variance with IFN-alpha, IFN-gamma directly stimulated M phi to synthesize and release IL 1, a monokine known to promote lymphocyte proliferation.
mesh_terms: D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D015232:Dinoprostone; D005260:Female; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011458:Prostaglandins E / Q000096:biosynthesis*; D013481:Superoxides / Q000378:metabolism
chemical_list: D001095:Arachidonic Acids; D007375:Interleukin-1; D011458:Prostaglandins E; D013481:Superoxides; D016718:Arachidonic Acid; D007371:Interferon-gamma; D015232:Dinoprostone