CLARITHROMYCIN SIGNIFICANTLY IMPROVES INTERLEUKIN-12-MEDIATED ANTI-MYCOBACTERIUM AVIUM ACTIVITY AND ABOLISHES TOXICITY IN MICE

Treatment of experimental murine Mycobacterium avium (MAC) infection w ith interleukin-12 (IL-12) significantly decreased MAC organisms in ti ssue but resulted in toxicity, Because IL-12-related toxicity was seen only in infected mice, IL-12 was combined with clarithromycin in an a ttempt to decrease bacterial burden. Clarithromycin (200 mg/kg/day) wa s administered alone to M. avium-infected mice for 1 week, and from we ek 2, IL-12 (20 mu g/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 w ith clarithromycin (P <.05), Clarithromycin plus IL-12 resulted in inc reased activity compared with either clarithromycin or IL-12 alone in reducing the number of bacteria in spleen and blood. Although potentia lly toxic, IL-12 is an effective immunotherapy for MAC infection, and combination with clarithromycin reduces IL-12 toxicity.