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-γ, TNF-α 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 mucosal leishmaniasis (ML). We evaluate the role of regulatory cytokines and cytokine antagonists in the downregulation 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-β) or antagonists of cytokines (α-TNF-α and α-IFN-γ). Cytokines production (IL-10, IL-17, TNF-α and IFN-γ) was measured by ELISA. IL-10 and TGF-β downmodulate TNF-α and IL-17 production, whereas IL-27 had no effect in the production of TNF-α, IFN-γ and IL-17 in these patients. Neutralization of TNF-α decreased IFN-γ level and the neutralization of IFN-γ decreased TNF-α level and increased IL-10 production. This study demonstrate that IL-10 and TGF-β 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-γ decreases the production of TNF-α in an IL-10-dependent manner.
Serviço de Imunologia, Hospital Universitário Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil; Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais INCT-DT (CNPq/MCT), Salvador, Bahia, Brazil.
Walker Nonato
WN
Oliveira
Serviço de Imunologia, Hospital Universitário Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil.
Luís Eduardo
LE
Ribeiro
Serviço de Imunologia, Hospital Universitário Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil; Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais INCT-DT (CNPq/MCT), Salvador, Bahia, Brazil.
Albert
A
Schrieffer
Serviço de Imunologia, Hospital Universitário Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil; Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais INCT-DT (CNPq/MCT), Salvador, Bahia, Brazil.
Paulo
P
Machado
Serviço de Imunologia, Hospital Universitário Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil; Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais INCT-DT (CNPq/MCT), Salvador, Bahia, Brazil.
Edgar M
EM
Carvalho
Serviço de Imunologia, Hospital Universitário Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil; Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais INCT-DT (CNPq/MCT), Salvador, Bahia, Brazil. Electronic address: olivinhaufba@gmail.com.
Olívia
O
Bacellar
D000328:Adult; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood / Q000494:pharmacology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000097:blood; D007378:Interleukins / Q000494:pharmacology; D007892:Leishmania braziliensis / Q000276:immunology* / Q000472:pathogenicity; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000097:blood*
C508609:IL10 protein, human; D020381:Interleukin-17; D007378:Interleukins; C464565:MYDGF protein, human; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma
Human american tegumentary leishmaniasis; Immunopathogenesis; Leishmania braziliensis; Regulatory cytokines