INHIBITION BY STREPTOMYCIN OF TUBERCLE-BACILLI WITHIN CULTURED HUMAN MACROPHAGES

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Abstract
The strategy for using streptomycin against tuberculosis assumes that it is not effective intracellularly. But according to animal cell experiments, this is probably incorrect. A new experimental model using cultured human macrophages infected with tubercle bacilli was used to retest this assumption so that the results would be directly relevant to human disease. At 5 and 50 .mu.g/ml, streptomycin inhibited the bacilli strongly and killed some. At the lowest tested concentration of 0.5 .mu.g/ml, it inhibited them weakly. It was acting intracellularly, because it could inhibit even when added 2 days after the macrophages had been infected and washed free of extracellular bacilli and in the experimental model the bacilli were shown to be unable to multiply extracellularly. However, as had been reported for animal macrophages, the antibiotic was quantitatively more than 2 orders of magnitude less effective in human macrophages than in simple bacteriologic medium. Probably because streptomycin is concentrated within lysosomes where low pH greatly inhibits it. The human macrophage-tubercle bacillus chemotherapeutic bioassay described here for the first time could be a superior patient-consonant method for testing antituberculosis agents and treatment regimens. It retains important in vivo features, the complete host cell-parasite relationship for instance, without giving up the in vitro advantages of rapidity and objectivity.