DIFFERENTIAL POTENTIATION OF ANTIMYCOBACTERIAL ACTIVITY AND REACTIVE NITROGEN INTERMEDIATE-PRODUCING ABILITY OF MURINE PERITONEAL-MACROPHAGES ACTIVATED BY INTERFERON-GAMMA (IFN-GAMMA) AND TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA)

The anti-mycobacterial activities of IFN-gamma and TNF-alpha-treated m urine peritoneal macrophages were determined. Resident macrophages pre treated with IFN-gamma or TNF-alpha for 2 days were infected with test organisms and subsequently cultured for up to 7 days. First, the earl y-phase growth of Mycobacterium tuberculosis (days 0-3) was strongly s uppressed in IFN-gamma-treated macrophages, and progressive bacterial elimination was subsequently observed. Although TNF-alpha treatment of macrophages did not affect the early phase growth of organisms, bacte rial killing was observed in the later phase of cultivation. Second, a lthough IFN-gamma-treated macrophages killed M. avium during the first 3 days of culture, regrowth of the intracellular organisms was subseq uently observed. TNF-alpha treatment of macrophages did not influence the mode of intracellular growth of M. avium. Third, IFN-gamma but not TNF-alpha enhanced production of reactive nitrogen intermediates (RNI ) by macrophages infected with M. tuberculosis or M. avium, whereas bo th cytokines increased macrophage release of reactive oxygen intermedi ates (ROI). The present findings therefore show that IFN-gamma and TNF -alpha potentiated the anti-mycobacterial activity of murine peritonea l macrophages in different fashions. They also suggest that RNI played more important roles than did ROI in the expression of macrophage ant i-mycobacterial, particularly anti-M. avium, activity.