Treatment with interleukin 12 in combination with atovaquone or clindamycin significantly increases survival of mice with acute toxoplasmosis.
The capacity of interleukin 12 (IL-12) to potentiate drugs in the treatment of murine toxoplasmosis was examined. IL-12 (100 ng/injection), atovaquone (10 mg/kg of body weight/day), or clindamycin (5 mg/kg/day) administered alone caused delayed time to death or minimal survival rates. In contrast, significant survival rates resulted when the same dose of IL-12 was used in combination the same doses of atovaquone (P=0.01) or clindamycin (P=0.001). Infected mice treated with IL-12 plus drug produced significantly higher levels of gamma interferon than controls. Although IL-12 was effective only when administered before infection, these results suggest that this cytokine may be a useful adjunct in the therapy of human toxoplasmosis in situations when cysts reactivate and tachyzoites start multiplying in immunocompromised patients.
Araujo
F G
FG
Research Institute, Palo Alto Medical Foundation, CA 94301, USA. ml.fga@forsythe.stanford.edu
Hunter
C A
CA
Remington
J S
JS
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D053626:Atovaquone; D002981:Clindamycin / Q000627:therapeutic use*; D004357:Drug Synergism; D005260:Female; D007371:Interferon-gamma / Q000032:analysis; D018664:Interleukin-12 / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D009285:Naphthoquinones / Q000627:therapeutic use*; D014124:Toxoplasmosis, Animal / Q000188:drug therapy* / Q000276:immunology
D000900:Anti-Bacterial Agents; D000981:Antiprotozoal Agents; D007376:Interleukin-2; D009285:Naphthoquinones; D018664:Interleukin-12; D015847:Interleukin-4; D002981:Clindamycin; D007371:Interferon-gamma; D053626:Atovaquone