Cytokines in the treatment of leishmaniasis: From studies of immunopathology to patient therapy

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Abstract
The genusLeishmania, an obligate intramacrophage parasite, causes a wide spectrum of clinical diseases. It is worldwide in distribution and causes 20 million new cases annually with an at risk population of approximately 1.5 billion persons. The most severe forms are associated with high morbidity, mortality and relapses with conventional therapy. The therapeutic issues and responses to standard and alternative therapies are reviewed. Recent developments in molecular biology and immunology methods employed in the study of leishmaniasis have defined an intricate interaction of the parasite with host immune system. Perturbation of the host immune responses may be part of the survival mechanisms ofLeishmania. In murine model, the finding of T helper cells that differ by their panel of cytokines has allowed a more precise definition of immunopathogenesis of leishmaniasis. Preliminary data from leishmaniasis patients lend support to this concept of altered immunomodulation. Furthermore, the enhancement of therapeutic response by interferon-γ has provided a new approach for treatment of patients using recombinant cytokines and for the study of the disease. Current research for early diagnosis, alternative therapies and need for vaccines are reviewed in the context of the immunopathology of leishmaniasis.