Alzheimer's disease and cytokine IL-10 gene polymorphisms: is there an association?

Alzheimer's disease (AD) is the most common form of dementia. In the last 15 years, a new theory has proposed the autoimmune mechanism as a trigger for AD. Studies on the association between AD and inflammatory biomarkers have yielded controversial results. Interleukin-10 (IL-10), an anti-inflammatory mediator, has been pointed out as one of the main cytokines associated with the occurrence of AD. Moreover, treatment that increases IL-10 levels could be a potential therapy for AD, since this cytokine acts on amyloid and pro-inflammatory molecule reduction. Based on the current literature, this study reviews evidence regarding the role of IL-10 polymorphisms in the context of AD, which has been shown to be of paramount importance for attenuating neuroinflammation, cognitive dysfunction and neurodegeneration.

Prognosis biomarkers evaluation in chronic lymphocytic leukemia.

OBJECTIVE/BACKGROUND: From clinical and biological points of view, chronic lymphocytic leukemia (CLL) is a heterogeneous disease characterized by a progressive accumulation of lymphocytes in the peripheral blood, bone marrow, and lymphoid organs. New prognostic markers in CLL may be useful to clinicians for predicting outcome and in clinical decision-making. The aim of this study was to evaluate the potential prognostic value of the apoptotic/survival-controlling proteins and protein tyrosine kinase ZAP-70 gene expression in CLL patients and control individuals, correlating such findings with patients' clinical data. METHODS: Fifty-three patients diagnosed with CLL attending the hematology service of a clinical hospital, and 24 healthy individuals with no history of leukemia (Control group) were enrolled in this study. Analyses of apoptotic/survival-controlling proteins were performed by western blot and ZAP-70 gene expression was evaluated by real-time polymerase chain reaction. RESULTS: Significant differences were observed for the p-p38, Mcl-1 long, and Mcl-1 short proteins when patients were compared with CLL and controls. A positive correlation between the results for Mcl-1 short and Mcl-1 long and lymphocyte count was observed, corroborating the hypothesis of an imbalance between proteins of cell survival pathways/apoptosis in CLL. CONCLUSION: ZAP-70 gene expression was not detected as a discriminant biomarker in these CLL patients. An imbalance between apoptosis-related proteins was observed in the present study, corroborating the hypothesis of increased survival of lymphocytes in CLL patients.

Two opposite extremes of adiposity similarly reduce inflammatory response of antigen-induced acute joint inflammation.

OBJECTIVE: Acute inflammation is a normal response of tissue to an injury. During this process, inflammatory mediators are produced and metabolic alterations occur. Adipose tissue is metabolically activated, and upon food consumption, it disrupts the inflammatory response. However, little is known about the acute inflammatory response in joints that results from diet-induced adipose tissue remodeling. The objective of this study was to determine whether alterations in adipose tissue mass arising from food consumption modify the inflammatory response of antigen-induced joint inflammation in mice. METHODS: Male BALB/c mice were fed a chow diet, a highly refined carbohydrate-containing (HC) diet for 8 wk. They were then immunized and, after 2 wk, received a knee injection of methylated bovine serum albumin (mBSA). They were sacrificed at 6, 24, and 48 h after injection. The effect of the cafeteria diet for 8 wk, which also increases adipose tissue, or conjugated linoleic acid (CLA) supplementation for 4 wk, a model of lipodystrophy, was evaluated 24 h after knee challenge with mBSA. RESULTS: Cellular influx, predominantly neutrophils, in synovial fluid was attenuated in the HC diet group, as were levels of myeloperoxidase and IL-1ß in periarticular tissue and histopathological analysis. These responses were associated with reduced adiponectin and increased leptin in serum, which was pronounced in mice fed the HC diet. Cafeteria diet and CLA supplementation induced a profile similar to that seen with the HC diet in terms of inflammation, disease response, and metabolic alteration. Interestingly, after the injection of mBSA, the area of adipocytes in the infrapatellar fat pad increased in mice fed with chow diet similar to those fed the HC and cafeteria diet. CONCLUSIONS: We demonstrated that attenuation of joint response induced by diet was independent of adipose tissue remodeling but could be associated with metabolic alterations.

Alzheimer's disease and cytokine IL-10 gene polymorphisms: is there an association? / A doença de Alzheimer e os polimorfismos no gene da citocina IL-10: há alguma associação?

ABSTRACT Alzheimer's disease (AD) is the most common form of dementia. In the last 15 years, a new theory has proposed the autoimmune mechanism as a trigger for AD. Studies on the association between AD and inflammatory biomarkers have yielded controversial results. Interleukin-10 (IL-10), an anti-inflammatory mediator, has been pointed out as one of the main cytokines associated with the occurrence of AD. Moreover, treatment that increases IL-10 levels could be a potential therapy for AD, since this cytokine acts on amyloid and pro-inflammatory molecule reduction. Based on the current literature, this study reviews evidence regarding the role of IL-10 polymorphisms in the context of AD, which has been shown to be of paramount importance for attenuating neuroinflammation, cognitive dysfunction and neurodegeneration.

RESUMO A doença de Alzheimer (DA) é a forma mais comum de demência. Nos últimos 15 anos, uma nova teoria propõe um mecanismo autoimmune como o gatilho para a DA. Associações entre DA e biomarcadores inflamatórios têm sido registradas, contudo com resultados controversos. A interleucina-10 (IL-10), um mediador anti-inflamatório, tem sido apontada como uma das principais citocinas associadas com a ocorrência de DA. Além disso, os tratamentos que aumentam os níveis de IL-10 podem ser uma terapia potencial para DA, uma vez que esta citocina atua sobre a redução de substância amiloide e de moléculas pró-inflamatórias. Baseando-se em literaturas atuais, este estudo revisa evidências relacionadas com o papel da IL-10 e seus polimorfismos no contexto da DA, o qual se mostrou ser de fundamental importância para atenuar a neuroinflamação, a disfunção cognitiva e a neurodegeneração.