Studies on the role of interleukin-12 in acute murine toxoplasmosis

Immunology. 1995 Jan;84(1):16-20.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Cell Division
  • Concanavalin A / pharmacology
  • Female
  • Immunity, Innate
  • Interferon-gamma / immunology
  • Interleukin-12 / administration & dosage
  • Interleukin-12 / immunology
  • Interleukin-12 / physiology*
  • Killer Cells, Natural / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID / immunology*
  • Nitrites / metabolism
  • T-Lymphocytes / cytology
  • Toxoplasmosis, Animal / immunology*
  • Toxoplasmosis, Animal / therapy
  • Tumor Necrosis Factor-alpha / immunology


  • Antibodies, Monoclonal
  • Nitrites
  • Tumor Necrosis Factor-alpha
  • Concanavalin A
  • Interleukin-12
  • Interferon-gamma