Journal of Antimicrobial Chemotherapy, Vol 39, 189-197, Copyright © 1997 by The British Society for Antimicrobial Chemotherapy
R Gomez-Flores, SD Tucker, R Kansal, R Tamez-Guerra and RT Mehta
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.
JOURNAL ARTICLE
Enhancement of antibacterial activity of clofazimine against Mycobacterium avium-Mycobacterium intracellulare complex infection induced by IFN-gamma is mediated by TNF-alpha
Department of Bioimmunotherapy, The University of Texas M. D. Anderson Cancer Center, Houston, USA.
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