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  • Title: Enhancement of antibacterial activity of clofazimine against Mycobacterium avium-Mycobacterium intracellulare complex infection induced by IFN-gamma is mediated by TNF-alpha.
    Author: Gomez-Flores R, Tucker SD, Kansal R, Tamez-Guerra R, Mehta RT.
    Journal: J Antimicrob Chemother; 1997 Feb; 39(2):189-97. PubMed ID: 9069539.
    Abstract:
    The effects of interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) alone or in combination with free or liposomal clofazimine against Mycobacterium avium-Mycobacterium intracellulare complex (MAC) were investigated. Treatment of murine resident peritoneal macrophages with 50 U/mL IFN-gamma (pre-infection) or 30 U/mL TNF-alpha (post-infection), caused significant reduction in intracellular MAC growth; this response was suppressed by anti-TNF-alpha antibodies or pentoxifylline. Activation of macrophages with IFN-gamma or TNF-alpha enhanced the intracellular activities of free and liposomal clofazimine against MAC; the individual antimycobacterial activities of free and liposomal clofazimine, however, were comparable. In the beige mouse model, IFN-gamma was ineffective, while liposomal clofazimine significantly decreased the infection in liver and spleen; the use of N(G)-monomethyl-L-arginine, a nitric oxide inhibitor, enhanced the effect of IFN-gamma against MAC infection. In addition, treatment of infected mice with either IFN-gamma or liposomal clofazimine significantly reduced the infection in peritoneal macrophages.
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