Inhibition of tubercle bacilli in cultured human macrophages by chloroquine used alone and in combination with streptomycin, isoniazid, pyrazinamide, and two metabolites of vitamin D3.
Intracellular tubercle bacilli (TB) reside in vacuoles in infected human macrophages (MPs). The relative impotency of streptomycin against TB in MPs and the contrary greatly increased potency of pyrazinamide (PZA) have been attributed to the fact that these vacuoles are phagolysosomes and, therefore, acidic. Chloroquine (CQ) is a lysomotropic base which can be used to raise phagolysosomal pH. Consequently, it was tested for its ability to increase the anti-TB effectiveness of streptomycin and decrease that of PZA in cultured human MPs. MPs infected with virulent Erdman strain TB were incubated in medium with various combinations of the drugs. Samples were taken at 0, 4, and 7 days and lysed for CFU counts of viable TB on nutrient agar. As expected, CQ increased the effectiveness of SM, but unexpectedly, it did not decrease that of PZA. CQ alone was found to be able to inhibit intracellular TB. Because of this, it was also tested with isoniazid, 1,25(OH)2-vitamin D3, and 25-OH-vitamin D3. It significantly enhanced the anti-TB protectiveness of both isoniazid and 25-OH-vitamin D3. Some combinations of CQ and the various drugs tested were able to kill intracellular TB. These results suggest that CQ may be useful in the treatment of tuberculosis.
Crowle
A J
AJ
Department of Microbiology and Immunology, University of Colorado Health Sciences Center, Denver 80262.
May
M H
MH
D000328:Adult; D002112:Calcifediol / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology*; D003470:Culture Media; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007538:Isoniazid / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D011718:Pyrazinamide / Q000494:pharmacology; D013307:Streptomycin / Q000494:pharmacology
D003470:Culture Media; D011718:Pyrazinamide; D002738:Chloroquine; D002117:Calcitriol; D002112:Calcifediol; D007538:Isoniazid; D013307:Streptomycin