BIDIRECTIONAL EFFECTS OF IFN-GAMMA ON GROWTH OF MYCOBACTERIUM-AVIUM COMPLEX IN MURINE PERITONEAL-MACROPHAGES

The effects of macrophage stimulation with interferon-gamma (IFN-gamma ) before or after infection on the intracellular growth of Mycobacteri um avium complex (MAC) were investigated, Treatment of murine peritone al macrophages before infection with IFN-gamma (50 U/ml) for 24 h and 48 h, but not for 72 h, was associated with 41% and 52% significant MA C growth inhibition, respectively, N-G-monomethyl-L-arginine (NMA) did not affect the preinfection antimycobacterial activity of IFN-gamma, thus indicating that nitric oxide was not involved in this phenomenon, In contrast, treatment of macrophages with IFN-gamma (50 U/ml) for 24 h and 48 h after infection was ineffective, whereas treatment for 72 h caused some MAC growth promotion, The use of NMA suppressed the IFN- gamma-mediated MAC growth, suggesting that nitric oxide may affect pos tinfection microbicidal function of macrophages, These results suggest that activation of macrophages with IFN-gamma before or after infecti on may direct the course of the infection and that nitric oxide may be detrimental more than beneficial for MAC-infected macrophages.