The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of human tegumentary leishmaniasis

In tegumentary leishmaniasis caused by Leishmania braziliensis, there is evidence that increased production of IFN-gamma, TNF-alpha and absence of IL-10 is associated with strong inflammatory reaction and with tissue destruction and development of the lesions observed in cutaneous leishmaniasis (CL) and mucosa] leishmaniasis (ML). We evaluate the role of regulatory cytokines and cytokine antagonists in the down-regulation of immune response in L braziliensis infection. Peripheral blood mononuclear cells from CL and ML were stimulated with soluble Leishmania antigen in the presence or absence of regulatory cytokines (IL-10, IL-27 and TGF-beta) or antagonists of cytokines (alpha-TNF-alpha, and alpha-IFN-gamma). Cytokines production (IL-10, IL-17, TNF-alpha, and IFN-gamma) was measured by ELISA. IL-10 and TGF-beta downmodulate TNF-alpha, and IL-17 production, whereas IL-27 had no effect in the production of TNF-alpha, IFN-gamma and IL-17 in these patients. Neutralization of TNF-alpha decreased IFN-gamma level and the neutralization of IFN-gamma decreased TNF-alpha, level and increased IL-10 production. This study demonstrate that IL-10 and TGF-beta are cytokines that appear to be more involved in modulation of immune response in CL and ML patients. IL-10 might have a protective role, since the neutralization of IFN-gamma decreases the production of TNF-alpha in an IL-10-dependent manner. (c) 2014 The Authors. Published by Elsevier Ltd. All rights reserved.