Influência da obesidade induzida por dieta hiperlipídica sobre a resposta imune em modelo experimental de alergia pulmonar

Abstract

Asthma and obesity are chronic inflammatory diseases with opposite immune profiles. Although, clinical and epidemiological studies reveal the association between them, as obese asthmatic individuals represent a distinct phenotype from the classic allergic asthma. However, the immune mechanisms involved in this association are not established yet, due to the lack of studies and the heterogeneity of the data obtained in experimental models. Therefore, the present study aimed to evaluate the influence of obesity over the immune response pulmonary allergic. Female Balb/c mice were fed with high fat diet during ten weeks so as to induce obesity. From the sixth to the tenth week of the protocol, PA and PA/OB groups were sensitized and challenged with ovalbumin. The following analyses were performed 24 and 48 hours after the last OVA challenge. Striking features of the allergic immune response were observed in the PA group, as elevated eosinophil count in BAL, lung tissue bone marrow, in association with high IL-4, IL-5, IL-9, IL-13, IL-25, IL-33, TSLP and anti-OVA IgE levels. There was also elevated production of CCL11 and EPO correlated with the eosinophilia. In contrast, IL-4, IL-5, TSLP and IL-25 levels were diminished in PA/OB group. In association with the reduced eosinophil count, low levels of CCL11, EPO and Anti-OVA IgE were detected. However, 48 hours after the last challenge, IL-1β, IL-4, IL-6, IL-9, IL-12, IL-13, IL-17A, TNF-α and IFN- level were higher in the PA/OB, the was also an increased M1 macrophage influx. There was also more neutrophils in the bone marrow and MPO in the lung tissue, indicating their increased influx to the lung of PA/OB animals. Mast cells and goblet cells count was increased in this group, 24 and 48 hours after the last challenge. Taken together these results suggest that obesity developed in BALB/c mice was able to influence the immune response in the lungs of animals after sensitization and challenge with allergen, interfering with the immune response classical Th2 and causing a delay in the development inflammatory immune response. Additionally, asthmatic obese animals showed exaggerated Th2 immune response, Th9 and high IL-17A levels associated with an increased influx of neutrophils into the lung and an intense mucus production, suggesting that these animals showed an allergy more severe inflammatory profile lung.