Effects of immunomodulators on acute Trypanosoma Cruzi infection in mice.
BACKGROUND
Patients who recover from acute trypanosomiasis may succumb to chronic Chagas' disease later in life due to age related immunosuppression, immune system disorders such 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 lethal Trypanosoma cruzi infection.


METHODS
ICR (Swiss) mice inoculated with Tulahuen (lethal) strain of 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 untreated animals. Mycophenolate mofetil (RS-61443) and recombinant interleukin-15 (IL-15) treatment decreased the number of parasites but had no effect on animal survival. In contrast, compound L-685-818 (tacrolimus analog) and CD40 ligand (CD40L), provided protection against lethal infection. Mice that survived initial infection were all protected against reinfection.


CONCLUSIONS
This study demonstrates the dangers of immunosuppression with tacrolimus and dexamethasone in T. cruzi infected subjects. While mycophenolate did not exacerbate the infection, our data suggest potential therapeutic applications for L-685-818 and CD40 ligand in trypanosomiasis.
Oz
Helieh S
HS
Department of Medicine, Division of GI/Hepatology, University of Louisville, Louisville, KY 40202, USA. helieh.oz@louisville.edu
Hughes
Walter T
WT
Thomas
Elaine K
EK
McClain
Craig J
CJ
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D023201:CD40 Ligand / Q000627:therapeutic use; D003907:Dexamethasone / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D019409:Interleukin-15 / Q000627:therapeutic use; D051379:Mice; D008813:Mice, Inbred ICR; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014349:Trypanosoma cruzi / Q000302:isolation & purification*; D014352:Trypanosomiasis / Q000188:drug therapy* / Q000469:parasitology
D000276:Adjuvants, Immunologic; D007166:Immunosuppressive Agents; D019409:Interleukin-15; C076383:L 685818; D023201:CD40 Ligand; D003907:Dexamethasone; D009173:Mycophenolic Acid; D016559:Tacrolimus