Clarithromycin significantly improves interleukin-12-mediated anti-Mycobacterium avium activity and abolishes toxicity in mice.
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.
Bermudez
L E
LE
Kuzell Institute for Arthritis and Infectious Diseases, California Pacific Medical Center Research Institute, San Francisco 94115, USA.
Petrofsky
M
M
Wu
M
M
Young
L S
LS
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000995:Antitubercular Agents / Q000627:therapeutic use* / Q000633:toxicity; D017291:Clarithromycin / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D018664:Interleukin-12 / Q000627:therapeutic use* / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D009162:Mycobacterium avium; D013154:Spleen / Q000378:metabolism; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D017291:Clarithromycin