Interferon decreases production of hydrogen peroxide by macrophages: correlation with reduction of suppressive capacity and of anti-microbial activity.
Mouse peritoneal macrophages (M phi) expressed enhanced tumoricidal activity upon in vitro stimulation either with the lymphokine M phi-activating factor (MAF) or with fibroblast interferon (IFN-beta). In contrast, M phi suppressive activity on lymphoproliferation was not affected by MAF pretreatment, but was drastically reduced or abolished by IFN-beta. Catalase, the enzyme involved in the destruction of hydrogen peroxide (H2O2), did significantly decrease M phi suppressive capacity but had no effect on M phi tumoricidal activity. Analysis of the phagocytosis-dependent H2O2 production by IFN-beta-treated M phi demonstrated a strong impairment of the oxygen metabolite release, which strictly paralleled the decreased M phi suppressive capacity. On the other hand, MAF did not modify H2O2 release by M phi. Studies on M phi antibacterial activity against Salmonella typhimurium, a function thought to depend upon H2O2 production, showed that exposure of M phi to IFN-beta significantly impaired their bactericidal and bacteriostatic capacity, again in close correlation with the decrease in H2O2 production. Thus, IFN-beta appears as modulating both suppressive and antibacterial capacities of M phi through reduction of their oxygen metabolism, whereas regulation of M phi anti-tumour activity is possibly controlled by different mechanisms.
D000818:Animals; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007108:Immune Tolerance; D007370:Interferon Type I / Q000494:pharmacology*; D008222:Lymphokines; D016215:Macrophage-Activating Factors; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000276:immunology; D010587:Phagocytosis; D012486:Salmonella typhimurium
D007370:Interferon Type I; D008222:Lymphokines; D016215:Macrophage-Activating Factors; D006861:Hydrogen Peroxide