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Clarithromycin significantly improves interleukin-12-mediated anti-Mycobacterium avium activity and abolishes toxicity in mice.
|Title||Clarithromycin significantly improves interleukin-12-mediated anti-Mycobacterium avium activity and abolishes toxicity in mice.|
|Publication Type||Journal Article|
|Year of Publication||1998|
|Authors||Bermudez LE, Petrofsky M, Wu M, Young LS|
|Journal||The Journal of infectious diseases|
|Date Published||1998 Sep|
|Keywords||Animals, Anti-Bacterial Agents, Antitubercular Agents, Clarithromycin, Dose-Response Relationship, Drug, Drug Therapy, Combination, Female, Interleukin-12, Mice, Mice, Inbred BALB C, Mycobacterium avium, Spleen, Tuberculosis, Tumor Necrosis Factor-alpha|
Treatment of experimental murine Mycobacterium avium (MAC) infection with interleukin-12 (IL-12) significantly decreased MAC organisms in tissue but resulted in toxicity. Because IL-12-related toxicity was seen only in infected mice, IL-12 was combined with clarithromycin in an attempt to decrease bacterial burden. Clarithromycin (200 mg/kg/day) was administered alone to M. avium-infected mice for 1 week, and from week 2, IL-12 (20 microg/kg twice per week) was added to the regimen for 4 weeks. Treatment with IL-12 resulted in 60% mortality, compared with 40% mortality in untreated control mice and 20% when IL-12 was given with clarithromycin (P < .05). Clarithromycin plus IL-12 resulted in increased activity compared with either clarithromycin or IL-12 alone in reducing the number of bacteria in spleen and blood. Although potentially toxic, IL-12 is an effective immunotherapy for MAC infection, and combination with clarithromycin reduces IL-12 toxicity.
|Alternate Journal||J. Infect. Dis.|