Tumor necrosis factor-independent protective effect of recombinant IFN-gamma against acute toxoplasmosis in T cell-deficient mice.
rIFN-gamma conferred remarkable resistance against acute infection with Toxoplasma gondii in T cell-deficient (athymic nude) mice. Mice that received an i.p. injection of rIFN-gamma every other day beginning 24 h before infection for a total of eight doses survived significantly longer than untreated control mice although all of the treated mice died after the lymphokine was discontinued. Mice that received 14 doses of rIFN-gamma survived significantly longer than those that received eight doses of the lymphokine although mice started dying soon after the final (14th) injection of rIFN-gamma and eventually all of the treated mice died. Histologic study revealed that the IFN-gamma treatment prevented proliferation of the organisms in all organs examined, including brain, lung, heart, liver, and spleen. The treatment was effective even when started 1 day after infection. Peritoneal macrophages obtained from mice injected with rIFN-gamma were activated and effectively killed tachyzoites of T. gondii in vitro. TNF activity could not be detected in sera of the infected mice during treatment with rIFN-gamma. Administration of anti-TNF antibody did not affect the protective effect of rIFN-gamma against T. gondii infection. These facts indicate that rIFN-gamma can confer resistance to acute infection with T. gondii without collaboration of lymphokines derived from T cells and TNF. This suggests that rIFN-gamma may be effective for therapy of toxoplasmosis in immunosuppressed patients who have impaired activity of T cell function, especially those with AIDS.
Department of Parasitology, Jikei University School of Medicine, Tokyo, Japan.
Y
Y
Suzuki
K
K
Joh
A
A
Kobayashi
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000502:physiology*
D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma