Avaliação da produção de interleucina 6, fator de necrose tumoral e interleucina 10 em hemoculturas de pacientes com Leishmaniose Cutânea localizada
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2017-03-10
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Universidade Federal de Goiás
Resumo
American 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.
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COSTA, A. C. V. Avaliação da produção de interleucina 6, fator de necrose tumoral e interleucina 10 em hemoculturas de pacientes com Leishmaniose Cutânea localizada. 2017. 101 f. Dissertação (Mestrado em Biologia da Relação Parasito-Hospedeiro) - Universidade Federal de Goiás, Goiânia, 2017.