The role of host factors for the chemotherapy of BCG infection in inbred strains of mice.
Host factors have previously been considered to play a role in the efficacy of "incomplete" antituberculous chemotherapy. We investigated this aspect using a model of intravenous infection with M. bovis-BCG in three inbred strains of mice. Viable splenic counts of bacilli (CFU) were monitored following a three week regimen of rifampicin (R) and isoniazid (H) given either immediately or from three weeks after infection. At the end of the immediate (0-3 weeks) therapy the spleens of all mice were sterile and only a minority of animals had demonstrable CFU's at 23 weeks after infection. However, following the delayed-onset (3-6 weeks) therapy we found a pronounced relapse of BCG growth which was about 10 times higher in CBA/Ca and BALB/C than in C57B1/6 mice. These results indicated that host immunity which developed during the first three weeks after infection may have aggravated the relapse of bacterial growth following chemotherapy. This interpretation was corroborated by the finding that the immunosuppressive drug cyclosporin given concurrently with R/H reduced the splenic viable counts of BCG.
Cox
J H
JH
MRC Tuberculosis and Related Infections Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, England.
Ivanyi
J
J
D000818:Animals; D003524:Cyclosporins / Q000494:pharmacology; D007109:Immunity / Q000187:drug effects; D007538:Isoniazid / Q000627:therapeutic use; D051379:Mice; D008815:Mice, Inbred Strains / Q000276:immunology; D009163:Mycobacterium bovis / Q000254:growth & development; D012293:Rifampin / Q000627:therapeutic use; D013997:Time Factors; D014376:Tuberculosis / Q000188:drug therapy / Q000276:immunology / Q000662:veterinary*
D003524:Cyclosporins; D007538:Isoniazid; D012293:Rifampin