title: Therapeutic enhancement of protective immunity during experimental leishmaniasis.
abstract: BACKGROUND
  Leishmaniasis remains a significant cause of morbidity and mortality in the tropics. Available therapies are problematic due to toxicity, treatment duration and emerging drug resistance. Mouse models of leishmaniasis have demonstrated that disease outcome depends critically on the balance between effector and regulatory CD4(+) T cell responses, something mirrored in descriptive studies of human disease. Recombinant IL-2/diphtheria toxin fusion protein (rIL-2/DTx), a drug that is FDA-approved for the treatment of cutaneous T cell lymphoma, has been reported to deplete regulatory CD4(+) T cells.
  
  
  RESULTS
  We investigated the potential efficacy of rIL-2/DTx as adjunctive therapy for experimental infection with Leishmania major. Treatment with rIL-2/DTx suppressed lesional regulatory T cell numbers and was associated with significantly increased antigen-specific IFN-γ production, enhanced lesion resolution and decreased parasite burden. Combined administration of rIL-2/DTx and sodium stibogluconate had additive biological and therapeutic effects, allowing for reduced duration or dose of sodium stibogluconate therapy.
  
  
  CONCLUSIONS
  These data suggest that pharmacological suppression of immune counterregulation using a commercially available drug originally developed for cancer therapy may have practical therapeutic utility in leishmaniasis. Rational reinvestigation of the efficacy of drugs approved for other indications in experimental models of neglected tropical diseases has promise in providing new candidates to the drug discovery pipeline.
authors: Division of Molecular Immunology, Cincinnati Children's Hospital Medical Center, and the University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.
authors: Senad
authors: S
authors: Divanovic
authors: Aurelien
authors: A
authors: Trompette
authors: Jamie I
authors: JI
authors: Ashworth
authors: Marepalli B
authors: MB
authors: Rao
authors: Christopher L
authors: CL
authors: Karp
mesh_terms: D000818:Animals; D000967:Antimony Sodium Gluconate / Q000008:administration & dosage*; D000981:Antiprotozoal Agents / Q000008:administration & dosage*; D001688:Biological Products / Q000008:administration & dosage*; D004167:Diphtheria Toxin / Q000008:administration & dosage*; D004359:Drug Therapy, Combination / Q000379:methods; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D007376:Interleukin-2 / Q000008:administration & dosage*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016896:Treatment Outcome
chemical_list: D000981:Antiprotozoal Agents; D001688:Biological Products; D004167:Diphtheria Toxin; D007155:Immunologic Factors; D007376:Interleukin-2; D000967:Antimony Sodium Gluconate