Effects of cyclosporin A on susceptibility and interferon-generating capacity in mice infected with Toxoplasma gondii.
Cyclosporin A (Cs-A), a potent immunosuppressant, was administered to mice to evaluate the role of T lymphocytes for the development of a protective immunity to an obligate intracellular protozoan parasite, Toxoplasma gondii. Although daily administration of various amounts of Cs-A for 7 days enhanced the host susceptibility at all doses employed, a dose-dependent manner of Cs-A treatment was not observed as far as the dosage regimens applied here are concerned; mice died at the same rate (40%) among the groups receiving various amounts of Cs-A. Cs-A treatment had a differential effect on the course of disease depending on how it was given in relation to infection. All mice receiving 50 mg of Cs-A per kg per day for 10 days from the beginning of infection eventually died of toxoplasmosis. Cs-A did not suppress the production of intereferon(IFN)-alpha/beta that was induced shortly after the infection, whereas it reduced greatly the ability of Toxoplasma-infected mice to produce IFN-gamma induced by stimulation with Toxoplasma lysate antigen (TLA). Moreover, the decrease in IFN-gamma production correlated with an increase in the parasitic growth in the peritoneal cavities of Cs-A-treated mice. These results suggest that the immunosuppressive effect of Cs-A on the primary Toxoplasma infection in mice is expressed by inhibiting the development of effector T cells responsible for the production of IFN-gamma.
Shirahata
T
T
Department of Veterinary Microbiology, Obihiro University of Agriculture and Veterinary Medicine, Hokkaido, Japan.
Katsuda
K
K
Ohta
C
C
Goto
H
H
D000818:Animals; D003524:Cyclosporins / Q000008:administration & dosage / Q000494:pharmacology*; D004198:Disease Susceptibility; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects; D007370:Interferon Type I / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000032:analysis / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051379:Mice; D008813:Mice, Inbred ICR; D009500:Neutralization Tests; D013601:T-Lymphocytes / Q000502:physiology*; D013997:Time Factors; D014122:Toxoplasma / Q000254:growth & development; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000378:metabolism / Q000401:mortality
D003524:Cyclosporins; D007370:Interferon Type I; D007371:Interferon-gamma