Clarithromycin significantly improves interleukin-12-mediated anti-Mycobacterium avium activity and abolishes toxicity in mice.

TitleClarithromycin significantly improves interleukin-12-mediated anti-Mycobacterium avium activity and abolishes toxicity in mice.
Publication TypeJournal Article
Year of Publication1998
AuthorsBermudez LE, Petrofsky M, Wu M, Young LS
JournalThe Journal of infectious diseases
Volume178
Issue3
Pagination896-9
Date Published1998 Sep
ISSN0022-1899
KeywordsAnimals, 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
Abstract

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 JournalJ. Infect. Dis.