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Dysregulated Network of Immune, Endocrine and Metabolic Markers is Associated to More Severe Human Chronic Chagas Cardiomyopathy.
Neuroimmunomodulation ( IF 2.2 ) Pub Date : 2018-09-27 , DOI: 10.1159/000491699
Florencia González 1 , Silvina Villar 1 , Luciano D'Attilio 1 , Rodolfo Leiva 2 , Julia Marquez 1 , Susana Lioi 3 , Juan Beloscar 2 , Oscar Bottasso 1 , Ana Rosa Perez 4
Affiliation  

Individuals who are infected with Trypanosoma cruzi develop chronic Chagas cardiomyopathy (CCC), which is a complication involving a series of immune pathogenetic mechanisms, although an association between immune and metabolic alterations was more recently proposed. Accordingly, we investigated the immuno-metabolic response in chagasic patients and their possible influence on CCC pathogenesis. To this end, T. cruzi-seropositive (asymptomatic or with CCC) and sero-negative individuals were studied. Serum tumour necrosis factor (TNF)-α, interleukin (IL)-6, adipocytokines and the expression of their receptors in peripheral blood mononuclear cell (PBMC) were evaluated, together with other factors influencing the immune response. CCC patients showed major metabolic and hormonal abnormalities, in parallel with increased IL-6 and leptin serum levels. TNF-α receptor s, leptin and adiponectin receptors (ObR and Adipo-Rs respectively), as well as PPAR-γ expression in PBMCs from CCC patients were compatible with a counteracting response leading to an unfavourable immune-metabolic profile. These results suggest that persistently increased levels of immune-metabolic pro-inflammatory mediators along with the adverse endocrine anti-inflammatory response of CCC individuals, may contribute to the underlying mechanisms dealing with myocardial tissue damage.

中文翻译:

免疫,内分泌和代谢标志物的网络失调与更严重的人类慢性南美锥虫性心肌病相关。

尽管最近提出了免疫和代谢改变之间的关联,但感染克氏锥虫的个体会发展为慢性恰加斯氏心肌病(CCC),这是一种涉及一系列免疫致病机制的并发症。因此,我们调查了chagasic患者的免疫代谢反应及其对CCC发病机制的可能影响。为此,研究了克氏锥虫血清阳性(无症状或伴有CCC)和血清阴性个体。评估了血清肿瘤坏死因子(TNF)-α,白介素(IL)-6,脂肪细胞因子及其受体在外周血单核细胞(PBMC)中的表达,以及其他影响免疫应答的因素。CCC患者显示出严重的代谢和激素异常,同时IL-6和瘦素血清水平升高。CCC患者的PBMC中的TNF-α受体,瘦素和脂联素受体(分别为ObR和Adipo-Rs)以及PPAR-γ表达与抵消反应相容,导致免疫代谢不良。这些结果表明,持续升高的免疫代谢促炎性介质水平以及CCC个体不良的内分泌抗炎反应,可能有助于处理心肌组织损伤的潜在机制。
更新日期:2019-11-01
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