Cytokine Therapy and Vaccination in Tropical Diseases (Leishmaniasis and Leprosy)

Abstract

The rationale for the immunotherapy applied in leishmaniasis and leprosy derives from the recent knowledge which has been gained from the pathophysiology of experimental leishmaniasis, i.e., from experiments with inbred mouse strains which are either resistant (e.g., C3He, C57BL/6) or susceptible (e.g., BALB/c) to infection with Leishmania major. These studies have shown that the outcome of the disease depends on the development of leishmania-specific CD4 cells into T-helper type-1 (Thl) cells in resistant mice or into T-helper type-2 (Th2) cells in susceptible mice (for a review, see [32]). The decisive factor is the cytokine profile released by these cells. Th2 cells release interleukin (IL)-4, IL-5, and IL-10, for example, which mediate progression of disease. Thl cells, in contrast, release exclusively IL-2 and interferon (IFN)-γ, by which the infection is successfully combated. IFN-γ, in particular, has potent effects, as it supports the further propagation of Thl cells and activates macrophages to kill the intracellular parasites. Macrophages are about the only cells which phagocytose the obligate intracellular leishmania. They therefore present the effector cells which, according to whether they are stimulated by Thl or Th2 cytokines, either eliminate the intracellular pathogen or allow its propagation. Consequently, the application of IFN-γ has been found to have beneficial effects in experimental leishmaniasis [32].