Clofazimine reverses the inhibitory effect of Mycobacterium tuberculosis derived factors on phagocyte intracellular killing mechanisms.
The effects of clofazimine on phagocyte functions associated with antimicrobial activity have been investigated. Clofazimine at a variety of concentrations was capable of enhancing the spontaneous production of hydrogen peroxide and the intracellular killing ability of phagocytes; but had no effect on resting phagocyte lysozyme release, or hexose monophosphate shunt (HMPS) activity. However, when these latter functions were assessed in the presence of a phagocytic stimulus, clofazimine moderately increased both lysozyme release and HMPS activity. A 25 Kd glyco-lipoprotein derived from Mycobacterium tuberculosis has been shown to inhibit these antimicrobial functions. Clofazimine was capable of partially reversing the inhibitory effect of the mycobacterial component in all of the systems assessed. Partial restoration was observed at concentrations of 0.5 mg/l and was maximal at 2 mg/l. These studies indicate important mechanisms operative in the pathogenesis of tuberculosis and suggest that clofazimine may have clinical relevance in the treatment of mycobacterial diseases.
D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D001770:Blood Bactericidal Activity / Q000187:drug effects*; D002176:Candida albicans / Q000276:immunology; D002991:Clofazimine / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000096:biosynthesis; D066298:In Vitro Techniques; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D009113:Muramidase / Q000096:biosynthesis; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D010427:Pentose Phosphate Pathway / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology
D001426:Bacterial Proteins; D006861:Hydrogen Peroxide; D002991:Clofazimine; D009113:Muramidase