Expressão de neuromediadores e sua correlação com o padrão fenotípico e funcional do infiltrado inflamatório de lesões de leishmaniose tegumentar americana causadas por Leishmania (Viannia) braziliensis / Expression of neuromediators and its correlation with the phenotypic and functional standard of the inflammatory infiltrated one of injuries of american tegumentary leishmaniasis caused for Leishmania (Viannia) braziliensis

AUTOR(ES)
DATA DE PUBLICAÇÃO

2008

RESUMO

American Tegumentary Leishmaniasis (ATL) is an important disease in Latin America and in Brazil, represents a serious public health problem. Localized cutaneous leishmaniasis (LCL) caused by Leishmania (Viannia) braziliensis tends to be, unlike mucosal forms (LM), susceptible to specific therapy and spontaneous healing occurs in a period of six to 12 months. However, a small group of patients did not achieve complete resolution of skin lesions, evolving in some cases with metastases, despite adequate treatment. Many data suggest that Leishmania infection in humans induces a cellular immune response characterized by a specific pattern of local production of cytokines and inflammatory mediators. This response could not only contribute to the resolution of the infection but also for the tissue damage. At the same time the abolition of the effector response could result in parasite persistence or even in the chronic disease. In our study the main was evaluate the inflammatory infiltrate of cutaneous lesions of ATL by L. (V.) braziliensis according cell subpopulations, cytokines and neuropeptides, the latter still not well characterized in the human infection. For that immunohistochemistry and real-time PCR techniques were used and the results were analyzed according to clinical form, response to antimonial therapy and illness duration. Our results showed that patients with poor response to therapy have a higher frequency of CD8+ T lymphocytes and an elevated production of the type 1 cytokines, such as IL-12 and IFNg, and TGF β and IL-10, when compared with patients with good response to therapy. Moreover, it was observed that patients with acute lesions had higher levels of IL-4 producing cells when compared to those with late lesions. A similar frequency of regulatory T lymphocytes (Foxp3+) was verified in all groups studied, but a significant decrease in their frequency in these groups was detected, when compared to the normal skin controls. The evaluation of neuromediators and other neuroproteins showed that LCL patients displayed an increase in β-NGF and GFAP synthesis, when compared to LM. There was also a greater production of the S-100 and PGP 9.5 in cases with poor response to treatment, while cases with good response presented high levels of CGRP. Despite Th1 response is considered essential for the control of infection, our data suggest that exacerbation of type 1 response, associated with the presence of TGF β and IL-10, could change the therapy response or could induce the maintenance of infection. Similarly the presence of neuromediators in injuries also appears to participate in ATL immunopatogenesis of ATL not only in the processes of neurogenic inflammation, but also in the mechanisms of healing and tissue remodeling.

ASSUNTO(S)

leishmaniose cutânea/terapia leishmaniasis cutaneous/transmission cytokines estudo comparativo leishmaniasis cutaneous/therapy humanos linfócitos t receptores de neurotransmissores t-lymphocytes leishmaniose cutânea/transmissão citocinas biologia molecular receptors, neurotransmitter

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