Influencia da obesidade no desenvolvimento da asma alergica experimental / Influence of obesity on allergic asthma development

AUTOR(ES)
DATA DE PUBLICAÇÃO

2009

RESUMO

Increases in eosinophil (EO) numbers in the tissues, blood, and bone marrow (BM) are a hallmark of asthma and, in general, elevated numbers correlate with disease severity. Epi-demiological data indicate that obesity increases the prevalence and incidence of allergic asthma. The basis for this relationship is unknown, but might be the result of common eti-ologies, comorbidities or genetic basis. Increased fat mass, particularly with central obesity, leads to production of cytokines and chemokines, such as IL-6, TNF-? and eotaxin. Studies have shown that genetically obese mice exhibit innate airway hyperresponsiveness, but little attention has been given to the allergic pulmonary EO recruitment in obese animals. Since selective accumulation of eosinophils into the airways has become a central concept of the asthma pathology, this study was designed to investigate the eosinophil influx into lungs and the role of Th2 cytokines in diet-induced obese mice. Four-week-old male C57bl6/J mice received a high fat diet for 10 weeks. On the eighth week, mice were sensi-tized with two s.c. ovalbumin (OVA) injections at 7 day intervals. One week thereafter, sensitized and non-sensitized animals were intranasally challenged with OVA. The mice were killed at different times (24, 48, 72 and 96 h) after OVA challenge, and EO counts in blood, bronchoalveolar lavage fluid (BAL) and BM were evaluated. High-fat diet mice ex-hibited a significant increase in body weight and epididymal fat, as well as increased total serum cholesterol levels compared with non-obese groups. Intranasal challenge with OVA in sensitized mice largely increased the EO counts in BAL at 48 h and 72 h post-OVA chal-lenge. Eosinophils were nearly absent in the non-sensitized mice. The sensitized obese mice showed a delayed EO emigration to BAL, peaking at 72 h post-OVA challenge. In addition, the morphological analysis showed that lung parenchyma of sensitized obese mice pre-sented a markedly higher EO infiltration at both 48 h and 72 h post-OVA challenge when compared with non-obese mice. In BM, a significant increase in counts of both mature and immature EO was also found in sensitized obese compared with sensitized non-obese mice. The levels of IL-4, IL-5, TNF-?, IL-6, IL-10 and eotaxin significantly increased in BAL of sensitized obese mice, peaking at 72 h-post OVA challenge. Our findings indicate that we have established an experimental model in C57bl6/J obese mice that clearly show a potentiation of EO influx in response to OVA challenge. In obese mice, EO are likely to be retained in the lung parenchyma exerting their effector functions in promoting the pathoge-nesis of airways diseases

ASSUNTO(S)

cytokine medula ossea obesidade asma asthma eosinophils obesity eosinofilos bone marrow citocinas

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