Gamma interferon suppresses acute and chronic Trypanosoma cruzi infection in cyclosporin-treated mice.
To determine if exogenous gamma interferon is effective in immunosuppressed mice infected with Trypanosoma cruzi, recombinant murine gamma interferon was administered to cyclosporin-treated mice with either acute or chronic T. cruzi infection. Gamma interferon significantly decreased parasitemia and prevented death in acutely infected mice. Parasitemias and mortality of mice treated with both gamma interferon and cyclosporin were similar to those of immunocompetent controls. In chronically infected mice, cyclosporin treatment produced significantly more organ explant cultures positive for T. cruzi. Fewer positive cultures, particularly for spleen and heart, were obtained from cyclosporin-treated mice when they also received gamma interferon. Ketoconazole treatment of mice resulted in no positive cultures. Cyclosporin treatment did not prevent activation of peritoneal macrophages by parenteral gamma interferon, nor did it have a consistent effect on serum titers of alpha/beta or gamma interferon in response to a second challenge inoculum of T. cruzi. These data indicate that exogenous gamma interferon suppresses acute and chronic T. cruzi infection in cyclosporin-treated mice but that gamma interferon is not as effective as the relatively specific antimicrobial ketoconazole. Gamma interferon activates macrophages despite cyclosporin treatment, and its effects appear to be tissue specific.
McCabe
R
R
Medical Service, Martinez Veterans Administration Medical Center, California 94553.
Meagher
S
S
Mullins
B
B
D000208:Acute Disease; D000818:Animals; D014355:Chagas Disease / Q000517:prevention & control*; D002908:Chronic Disease; D003524:Cyclosporins / Q000494:pharmacology*; D007371:Interferon-gamma / Q000097:blood / Q000627:therapeutic use*; D007654:Ketoconazole / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D011994:Recombinant Proteins
D003524:Cyclosporins; D011994:Recombinant Proteins; D007371:Interferon-gamma; D007654:Ketoconazole