Recombinant interferon-gamma and chemotherapy with isoniazid and rifampicin in experimental murine tuberculosis

Viable bacterial counts in the lungs and spleens of mice infected intravenously with Mycobacterium tuberculosis, strain H37Rv were reduced by intravenous recombinant murine interferon-gamma (IFN-gamma) 1000-5000 u, but not by 200 u. Reduction in counts was greatest when IFN-gamma was given 1 day before infection and was not increased by additional doses in the preceding 2 days. The effect was complete in 1 day and was not increased by successive doses during the next week. Giving IFN-gamma in multilamellar liposomes further reduced the spleen viable counts, but this appeared due to the liposomes themselves and not to encapsulation of IFN-gamma within them. Only a minimal reduction in organ viable counts, not statistically significant, occurred when IFN-gamma was given 5 days after infection. Although IFN-gamma alone and isoniazid 25 mg/kg alone reduced the organ viable counts, combined treatment with IFN-gamma and isoniazid was no more bactericidal than isoniazid alone. Similarly, the bactericidal activity of rifampicin 25 mg/kg was not increased by simultaneous administration of IFN-gamma. There seems little likelihood that IFN-gamma would increase the efficacy of the early stages of the chemotherapy of tuberculosis.