BackgroundThe interleukin 32 (IL-32) is a proinflammatory cytokine produced by immune and non-immune cells. It can be induced during bacterial and viral infections, but its production was never investigated in protozoan infections. American Tegumentary Leishmaniasis (ATL) is caused by Leishmania protozoan leading to cutaneous, nasal or oral lesions. The aim of this study was to evaluate the expression of IL-32 in cutaneous and mucosal lesions as well as in peripheral blood mononuclear cells (PBMC) exposed to Leishmania (Viannia) braziliensis.MethodsIL-32, tumour necrosis factor (TNF) and IL-10 protein expression was evaluated by immunohistochemistry in cutaneous, mucosal lesions and compared to healthy specimens. The isoforms of IL-32α, β, δ, γ mRNA, TNF mRNA and IL-10 mRNA were assessed by qPCR in tissue biopsies of lesions and healthy skin and mucosa. In addition, PBMC from healthy donors were cultured with amastigotes of L. (V.) braziliensis. In lesions, the parasite subgenus was identified by PCR-RFLP.ResultsWe showed that the mRNA expression of IL-32, in particular IL-32γ was similarly up-regulated in lesions of cutaneous (CL) or mucosal (ML) leishmaniasis patients. IL-32 protein was produced by epithelial, endothelial, mononuclear cells and giant cells. The IL-32 protein expression was associated with TNF in ML but not in CL. IL-32 was not associated with IL-10 in both CL and ML. Expression of TNF mRNA was higher in ML than in CL lesions, however levels of IL-10 mRNA were similar in both clinical forms. In all lesions in which the parasite was detected, L. (Viannia) subgenus was identified. Interestingly, L. (V.) braziliensis induced only IL-32γ mRNA expression in PBMC from healthy individuals.ConclusionsThese data suggest that IL-32 plays a major role in the inflammatory process caused by L. (Viannia) sp or that IL-32 is crucial for controlling the L. (Viannia) sp infection.

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Leishmania (Viannia) braziliensis causes cutaneous and mucosal leishmaniasis in several countries in Latin America. In mammals, the parasites live as amastigotes, interacting with host immune cells and stimulating cytokine production that will drive the type of the specific immune responses. Generation of Th17 lymphocytes is associated with tissue destruction and depends on IL-1β, IL-6, TGF-β and IL-23 production, whereas IL-10 and TGF-β are associated with tissue protection. Here, we evaluate whether amastigotes stimulate peripheral blood mononuclear cells (PBMCs) from healthy donors to produce the major cytokines responsible for the generation of Th17. Seven L. (V.) braziliensis isolates from patients with different clinical forms of leishmaniasis were expanded in interferon-γ knockout mice to obtain amastigotes and in culture to get promastigotes. The parasites were used to stimulate PBMCs from healthy donors, and cytokine production was evaluated by ELISA or qPCR. Amastigotes and promastigotes induced IL-10 production in PBMCs; however, only amastigotes induced IL-1β, IL-6 and TGF-β. These data demonstrate for the first time that L. (V.) braziliensis amastigotes directly stimulate production of a unique pattern of cytokines that could contribute to the generation of Th17.

Resumo: a obesidade comumente é associada com outras doenças como: hipertensão arterial, diabetes mellitus tipo II, cardiovasculares e inflamação crônica. Estudos demonstram o tecido adiposo (TA) como um órgão endócrino capaz de influenciar a homeostase energética e hemodinâmica, além de ter papel importante na resposta inflamatória. O termo adipocina é utilizado para nomear peptídeos bioativos sintetizados e secretados por adipócitos. O interesse em estudar essas proteínas teve início com a descoberta da leptina e suas diversas funções, hoje já sabemos que o TA secreta outros hormônios, proteínas de fase aguda, quimiocinas, fatores hemostáticos e hemodinâmicos e fatores de crescimento. Este trabalho teve por objetivo estudar os principais grupos de adipocinas visando uma maior compreensão de seus mecanismos de ação, das finalidades e influências no desenvolvimento da obesidade e estado de inflamação crônica. Foi observado que essas adipocinas em desequilíbrio promovem impacto em diversas funções corporais, alterando a ingesta alimentar, sensibilidade à insulina, resposta imune, angiogênese, pressão arterial, metabolismo lipídico e balanço energético. Dessa maneira se faz necessária uma compreensão dos efeitos do tratamento como atividade física, nutrição, aspecto psicológico e clínica sobre o controle hormonal e de citocinas, a fim de se desenvolver terapias mais eficazes, diminuindo as complicações da obesidade. Palavras-chave: Adipocinas. Leptina. Adiponectina. Resistina. Obesidade.Abstract: the obesity is commonly associated with other diseases such as hypertension, diabetes mellitus type II, cardiovascular and chronic inflammation. Studies revealed adipose tissue (AT) as an endocrine organ capable of influencing the energy and hemodynamic homeostasis, and play an important role in the inflammatory response. The adipokine term is used to name bioactive peptides synthesized and secreted by adipocytes. The interest in studying these proteins began with the discovery of leptin and its various functions, today we know that the TA secret other hormones, acute phase proteins, chemokines, hemostatic and hemodynamic factors and growth factors. This study aims to investigate the major adipokines groups seeking a greater understanding of their mechanisms of action, its purposes and influences the development of obesity and chronic state of inflammation. It was observed that these imbalance adipokines have a impact on several body functions, altering dietary intake, insulin sensitivity, immune response, angiogenesis, blood pressure, lipid metabolism and energy. Thus, a understanding of the effects of treatment such as physical activity, nutrition, psychological and clinical aspects on hormonal and cytokine control is necessary in order to develop more effective therapies, reducing the complications of obesity.

Human leishmaniasis caused by Leishmania (Viannia) braziliensis can be presented as localized cutaneous leishmaniasis (LCL) or mucosal leishmaniasis (ML). Macrophages kill parasites using nitric oxide (NO) and reactive oxygen species (ROS). The aim of this study was to evaluate the ability of parasites obtained from patients with LCL or ML to produce and resist NO or ROS. Promastigotes and amastigotes from LCL or ML isolates produced similar amounts of NO in culture. Promastigotes from ML isolates were more resistant to NO and HO than LCL parasites in a stationary phase, whereas amastigotes from LCL isolates were more resistant to NO. In addition, in the stationary phase, promastigote isolates from patients with ML expressed more thiol-specific antioxidant protein (TSA) than LCL isolates. Therefore it is suggested that infective promastigotes from ML isolates are more resistant to microbicidal mechanisms in the initial phase of infection. Subsequently, amastigotes lose this resistance. This behavior of ML parasites can decrease the number of parasites capable of stimulating the host immune response shortly after the infection establishment.