Potential Use of Interleukin-10 Blockade as a Therapeutic Strategy in Human Cutaneous Leishmaniasis

白细胞介素-10 阻断剂作为人类皮肤利什曼病治疗策略的潜在用途

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作者:Lucio Roberto Castellano, Laurent Argiro, Helia Dessein, Alain Dessein, Marcos Vinícius da Silva, Dalmo Correia, Virmondes Rodrigues

Abstract

Interleukin-10 overproduction has been associated with worse prognosis in human cutaneous leishmaniasis, while IFN-γ-dependent responses are associated with parasite killing and host protection. Innovative strategies are needed to overcome therapeutic failure observed in endemic areas. The use of monoclonal antibody-based immunotherapy targeting IL-10 cytokine was evaluated here. Partial IL-10 blockade in Leishmania braziliensis whole soluble antigen-stimulated cells from endemic area CL patients with active or healed lesions and asymptomatic controls was evaluated. Overall decrease in IL-10, IL-4, and TNF-α production was observed in all groups of subjects. Only patients with active lesions still produced some levels of TNF-α after anti-IL-10 stimulation in association with Leishmania antigens. Moreover, this strategy showed limited modulatory effects on IFN-γ-dependent chemokine CXCL10 production. Results suggest the potential immunotherapeutic use of partial IL-10 blockade in localized cutaneous leishmaniasis.

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