Abstract

BACKGROUND: Patients who recover from acute trypanosomiasis may succumbto chronic Chagas' disease later in life due to age related immunosuppression, immune system disorderssuch as AIDS, or during periods of immunosuppressive therapy for organ transplantation. In this study,effects of immunomodulators with diverse properties were examined on the course of an acute and lethalTrypanosoma cruzi infection.MATERIAL/METHODS: ICR (Swiss) mice inoculated with Tulahuen (lethal) strainof T. cruzi were treated with 6 different immunomodulators and the course of infection was studied.RESULTS:Tacrolimus (FK-506) and dexamethasone increased parasitemia in mice when compared to infected untreatedanimals. Mycophenolate mofetil (RS-61443) and recombinant interleukin-15 (IL-15) treatment decreasedthe number of parasites but had no effect on animal survival. In contrast, compound L-685-818 (tacrolimusanalog) and CD40 ligand (CD40L), provided protection against lethal infection. Mice that survived initialinfection were all protected against reinfection.CONCLUSIONS: This study demonstrates the dangers ofimmunosuppression with tacrolimus and dexamethasone in T. cruzi infected subjects. While mycophenolatedid not exacerbate the infection, our data suggest potential therapeutic applications for L-685-818 andCD40 ligand in trypanosomiasis.

Keywords: Adjuvants, Immunologic, CD40 Ligand, Dexamethasone, Immunosuppressive Agents, Interleukin-15, Mice, Inbred ICR, Mycophenolic Acid, Research Support, Non-U.S. Gov, Research Support, U.S. Gov, Research Support, U.S. Gov, Tacrolimus, Trypanosoma cruzi, Trypanosomiasis