Studies on the role of interleukin-12 in acute murine toxoplasmosis.
Interleukin-12 (IL-12) is important in the regulation of resistance to Toxoplasma gondii in mice with severe combined immunodeficiency (SCID). The protective ability of IL-12 in SCID mice appears to be through its activity on natural killer (NK) cells to induce production of interferon-gamma (IFN-gamma). In this study we assessed the role of IL-12 in the acute stage of toxoplasmosis in immunocompetent mice. Administration of IL-12 to BALB/c mice infected with the virulent C56 strain of T. gondii remarkably delayed time to death. The protective activity of IL-12 was abrogated by administration of monoclonal antibodies to IFN-gamma or tumour necrosis factor-alpha (TNF-alpha), and by depletion of NK cells using an antisera against asialoGM1. Whereas BALB/c mice infected with the ME49 strain of T. gondii survived infection, administration of anti-IL-12 to infected mice resulted in 100% mortality accompanied by decreased serum levels of IFN-gamma. Furthermore, this treatment significantly reversed the suppression of spleen cell proliferation to concanavalin A (Con A), which is associated with the acute stage of infection, and resulted in decreased ex vivo production of IFN-gamma, IL-2, IL-4 and IL-10 in response to Con A. Our results indicate an important role for IL-12 in mediating resistance to T. gondii during acute infection in immunocompetent mice, that NK cells are required for this protective activity, and that IL-12 is involved in the immunosuppression which accompanies this infection.
Hunter
C A
CA
Research Institute, Palo Alto Medical Foundation, CA 94301.
Candolfi
E
E
Subauste
C
C
Van Cleave
V
V
Remington
J S
JS
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D002455:Cell Division; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000008:administration & dosage / Q000276:immunology / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID / Q000276:immunology*; D009573:Nitrites / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000628:therapy; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000911:Antibodies, Monoclonal; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D018664:Interleukin-12; D007371:Interferon-gamma