Drug Potentiation of Macrophage Function

Abstract

The mechanism by which macrophages kill facultative intracellular parasites is not known. A test system is described utilizing human macrophages derived from blood monocytes and the opportunistic pathogen Listeria monocytogenes . In this system, bacterial killing was impaired under hypoxic conditions. Under aerobic conditions, addition of Clofazimine (B663), a phenazine derivative effective in the treatment of human leprosy, potentiated the killing of Listeria by macrophages. Potentiation occurred at drug concentrations usually attainable in man and which are not directly injurious to the bacteria. The enhanced bactericidal activity occurred only in the presence of oxygen; the drug induced increased leukocyte oxygen consumption which was insensitive to cyanide.