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 Mycobacterium avium complex (MAC) were investigated. Treatment of murine peritoneal 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 MAC growth inhibition, respectively. NG-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 postinfection microbicidal function of macrophages. These results suggest that activation of macrophages with IFN-gamma before or after infection may direct the course of the infection and that nitric oxide may be detrimental more than beneficial for MAC-infected macrophages.