CYTOKINES IN THE TREATMENT OF LEISHMANIASIS - FROM STUDIES OF IMMUNOPATHOLOGY TO PATIENT THERAPY

The genus Leishmania, an obligate intramacrophage parasite, causes a w ide spectrum of clinical diseases. It is worldwide in distribution and causes 20 million new cases annually with an at risk population of ap proximately 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 ther apies are reviewed. Recent developments in molecular biology and immun ology methods employed in the study of leishmaniasis have defined an i ntricate interaction of the parasite with host immune system. Perturba tion of the host immune responses may be part of the survival mechanis ms of Leishmania. In murine model, the finding of T helper cells that differ by their panel of cytokines has allowed a more precise definiti on of immunopathogenesis of leishmaniasis. Preliminary data from leish maniasis patients lend support to this concept of altered immunomodula tion. Furthermore, the enhancement of therapeutic response by interfer on-gamma has provided a new approach for treatment of patients using r ecombinant cytokines and for the study of the disease. Current researc h for early diagnosis, alternative therapies and need for vaccines are reviewed in the context of the immunopathology of leishmaniasis.