INVIVO CYTOKINE PROFILES IN PATIENTS WITH KALA-AZAR - MARKED ELEVATION OF BOTH INTERLEUKIN-10 AND INTERFERON-GAMMA

The immunological mechanisms underlying the susceptibility to dissemin ated visceral parasitism of mononuclear phagocytes in patients with ka la-azar remain undefined. Resistance and susceptibility are correlated with distinct patterns of cytokine production in murine models of dis seminated leishmanial disease. To assess lesional cytokine profiles in patients with kala-azar, bone marrow aspirates were analyzed using a quantitative reverse transcriptase PCR technique to amplify specific m RNA sequences of multiple Th1-, Th2-, and/or macrophage-associated cyt okines. Transcript levels of IL-10 as well as IFN-gamma were significa ntly elevated in patients with active visceral leishmaniasis; IL-10 le vels decreased markedly with resolution of disease. These findings sug gest that IL-10, a potent, pleiotropic suppressor of all known microbi cidal effector functions of macrophages, may contribute to the pathoge nesis of kala-azar by inhibiting the cytokine-mediated activation of h ost macrophages that is necessary for the control of leishmanial infec tion.