Obesidade e esofagite eosinofílica: caracterização imunopatológica e efeito do tratamento com cromoglicato de sódio

Abstract

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease that presents clinical symptoms such as dysphagia, vomiting, food impaction, retrosternal and epigastric pain. The immune response in EoE is characterized by elevated serum levels of antigen-specific IgE and a Th2 immune response profile, with increased IL-4 and IL-5 cytokines. It is a difficult to diagnose disease and so to treat. Its prevalence has been significantly increased in the recent decades around the world. Lifestyle changing is among the several factors that may be contributing to this increasing, especially when related to eating habits and sedentarism. Related to it there is obesity, a chronic and systemic inflammatory disease characterized by elevated levels of proinflammatory cytokines. It is believed that this inflammation participates in the etiology of various autoimmune and allergic diseases. However, there are no studies in the literature to evaluate whether obesity has any influence on the development or worsening of eosinophilic inflammation of EoE. Therefore, the present study aimed to evaluate obesity influence and treatment effect with sodium cromoglycate (CG) on the immune response in the EoE. For this male Balb/c mice were used, in which obesity was induced by a hyperlipid diet for ten weeks. There was also EoE model induction, which occurred by subcutaneous administration and ovalbumin (OVA) oral challenges. GC treatment was concomitant with the allergy induction protocol. The hyperlipid diet has promoted increased body mass, accumulation of perigonadal fat, and increased fasting glycemia, triglycerides (TG), total cholesterol (Col), HDL-cholesterol (HDL-C), and LDL-cholesterol (low density lipoprotein - LDL-C), TNF-α and leptin. Obesity promoted a greater increase in mast cells on the animals in the group, also an increase of eosinophils and tissue remodeling accompanied by higher TSLP mRNA expression, Foxp3 lower expression and IL-10 mRNA, after the OVA challenge, when compared to the lean allergic group. Esophageal tissue cell accumulation was associated with a larger number of Th2 lymphocytes, CD11c+MHChiCD80+, in both peripheral lymphoid organs. In contrast, there was a reduction in the number of DCs CD11c+MHChi+PDL1+ and B CD19+CD40+ lymphocytes in the spleen. Antigen-specific IgE levels were reduced in obese allergic animals compared to lean allergic individuals. Obese animals have presented an increase in mast cells and eosinophils independently of allergy induction. Treatment with CG has reduced the number of mast cells, eosinophils and tissue remodeling. It also had induced the increasing of CD3+CD4+CD25+Foxp3+ regulatory T cells in both lymphoid organs and increased the expression of IL-10 mRNA in the esophageal tissue. Thus, obesity has increased the risk of development and worsening of EoE, mediated by the imbalance between regulatory mechanisms and effectors. These data provide new insight into another risk factor for EoE, contributing to future treatment strategies in specific patient subgroups. It also reinforced the protective effect of sodium cromoglycate, which could be used as a more therapeutic approach in the prevention and treatment of EoE.