The effects of cyclosporine on Toxoplasma gondii in vivo and in vitro.
We examined the effect of cyclosporine on Toxoplasma infection in vivo and in vitro. Administration to mice of 150 mg/kg/day cyclosporine variably affected mortality in four separate experiments. IgG (Sabin-Feldman dye test) and IgM enzyme-linked immunosorbent assay antibody titers were significantly depressed in mice treated with cyclosporine. These results suggested the possibility that cyclosporine possesses anti-Toxoplasma activity. Thus, macrophages were incubated with cyclosporine before and after infection with Toxoplasma. Treatment with 0.5, 1, and 5 micrograms cyclosporine/ml during or after challenge of macrophage monolayers with Toxoplasma inhibited replication of Toxoplasma (and resulted in killing of Toxoplasma). The effect of cyclosporine on development of activated macrophages was studied. Cyclosporine administered to mice at a dose of 150 mg/kg/day neither accelerated nor delayed activation of macrophages (assessed by inhibition of Toxoplasma replication in vitro) by i.v. injection of either Corynebacterium parvum or Toxoplasma. Cyclosporine affects mortality variably in murine toxoplasmosis, depresses synthesis of IgG and IgM Toxoplasma antibody in vivo, does not prevent activation of macrophages in vivo, and possesses anti-Toxoplasma activity in vitro and perhaps in vivo. Cyclosporine may be the preferred immunosuppressive agent for recipients of an organ transplant who are at high risk for toxoplasmosis (e.g., seronegative recipients who have received organ from seropositive donors).
R E
RE
McCabe
B J
BJ
Luft
J S
JS
Remington
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D003524:Cyclosporins / Q000494:pharmacology*; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000469:parasitology; D051379:Mice; D014122:Toxoplasma / Q000187:drug effects / Q000254:growth & development; D014124:Toxoplasmosis, Animal / Q000276:immunology / Q000469:parasitology*
D003524:Cyclosporins; D007074:Immunoglobulin G; D007075:Immunoglobulin M