Programa de Pós-graduação em Biologia da Relação Parasito-Hospedeiro
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Item Avaliação da produção de interleucina 6, fator de necrose tumoral e interleucina 10 em hemoculturas de pacientes com Leishmaniose Cutânea localizada(Universidade Federal de Goiás, 2017-03-10) Costa, Ana Carolina Vieira da; Dias, Fátima Ribeiro; http://lattes.cnpq.br/5741031258926403; Dias, Fátima Ribeiro; http://lattes.cnpq.br/5741031258926403; Cardoso, Ludimila Paula Vaz; Pereira, Ledice Inacia de AraujoAmerican Tegumentary Leishmaniasis (ATL) is caused by protozoa of the genus Leishmania. The parasite is hosted by macrophages in cutaneous or mucosal lesions. Monocytes are precursors of macrophages, but there is little information about monocyte activation during ATL. The present study aimed to evaluate cytokine profile of monocytes from patients with localized cutaneous leishmaniasis (LCL) in whole blood cultures stimulated with toll-like receptor (TLRs) and NOD2 receptor agonists. Peripheral blood from patients with active lesions and no treatment, and from healthy blood donors paired by sex and age, was diluted into culture medium and incubated with lipopolysaccharide (LPS), TLR4 agonist; lipopeptide Pam3Cys (Pam), TLR2 agonist; muramyldipeptide (MDP), NOD2 agonist or Leishmania (V.) braziliensis antigen (Ag). After incubation, supernatants were collected to measure IL-6 and TNF (6 h) and IL-10 (24 h) by ELISA. There was production of IL-6, TNF and IL-10 in cultures from patients and controls after stimulation with all agonists and Ag (p < 0.05, medium vs stimulus, n = 29). No differences were detected between concentrations of TNF and IL-10, but IL-6 was higher produced in non-stimulated cultures from patients than controls (p < 0.05, n = 29) or when the stimulus was MDP (p < 0.05, n = 19). The combination Pam/MDP increased the production of IL-6, TNF and IL-10 in cultures from patients and controls when compared with each stimulus isolated (p < 0.05, n = 13 - 14); similarly, Ag and MDP together induced higher concentrations of IL-6, TNF and IL-10 (IL-6 and IL-10, especially in cultures from patients) in comparison with each stimulus (p < 0.05, n = 11 - 14). There was no correlation between the number, size or time of lesions and levels of IL-6, TNF or IL-10. Patients with more than one cycle of treatment to obtain clinical cure showed higher levels of MDP-induced IL-6 than those cured with one cycle of treatment (p < 0.05, n = 17 cured with one cycle vs 8 cured with more than one cycle). Data suggest that LCL patient monocytes can be activated via TLR2, TLR4 or NOD2 to produce pro-inflammatory (IL-6, TNF) and anti-inflammatory (IL-10) cytokines and IL-6 can be associated with tissue lesion and delay of lesion healing indicating an immunopathogenic role in LCL.