Disodium cromoglycate treatment reduces TH2 immune response and immunohistopathological features in a murine model of Eosinophilic Esophagitis

Int Immunopharmacol. 2020 Jun:83:106422. doi: 10.1016/j.intimp.2020.106422. Epub 2020 Apr 3.

Abstract

Eosinophilic esophagitis (EoE) is an emergent chronic disease of the esophagus. The immunopathological process in EoE is characterized by Th2 immune response and prominent eosinophilic influx, in response to common food allergens. The classical treatment consists of allergen elimination diet and systemic/topical corticosteroid therapy. Nevertheless, patients do not always comply to treatment, and the prolonged corticosteroid therapy can cause side effects, therefore, there is an immediate need for new therapeutic approach for EoE. Disodium cromoglicate (DSCG) is a substance broadly used in allergic asthma treatment, and a well-known mast cell activation stabilizer. However, its effect in EoE have not been evaluated yet. This study aimed to assess the effects of DSCG treatment in an EoE experimental model. Male Balb/C mice were subcutaneously sensitized for five days with OVA, and subsequently orally OVA-challenged, DSCG administration was performed between the OVA-challenges. DSCG treatment not only reduced eosinophilic and mast cell influx, as well as reduced fibrosis. In addition, tslp, GATA3, IL-5, FoxP3 and IL-10 mRNA expression were reduced in esophageal mucosa, associated with lower Th2 (CD3+CD4+GATA3+IL4+) and B cells (CD19+CD40+) number in peripheral lymphoid organs. In conclusion, the data demonstrate DSCG treatment was effective in reducing mast cell activation and Th2 immune response, important immunopathological EoE features. Therefore, the use of DSCG as an EoE treatment can be considered a promising therapeutic approach to treat this disease.

Keywords: Allergy; Disodium cromoglycate; Eosinophilic esophagitis; Immune response; Inflammation.

MeSH terms

  • Animals
  • Bone Marrow / drug effects
  • Bone Marrow / immunology
  • Bone Marrow / pathology
  • Cromolyn Sodium / pharmacology*
  • Disease Models, Animal
  • Eosinophilic Esophagitis / chemically induced
  • Eosinophilic Esophagitis / drug therapy
  • Eosinophilic Esophagitis / immunology*
  • Eosinophilic Esophagitis / pathology
  • Eosinophils / drug effects
  • Eosinophils / immunology
  • Esophageal Mucosa / drug effects
  • Esophageal Mucosa / immunology
  • Esophageal Mucosa / pathology
  • Fibrosis / immunology
  • Fibrosis / pathology
  • Immunity / drug effects
  • Immunity / immunology
  • Lymphoid Tissue / drug effects
  • Lymphoid Tissue / immunology
  • Male
  • Mast Cell Stabilizers / pharmacology*
  • Mast Cells / drug effects
  • Mast Cells / immunology
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / toxicity
  • Th2 Cells / drug effects*
  • Th2 Cells / immunology*

Substances

  • Mast Cell Stabilizers
  • Ovalbumin
  • Cromolyn Sodium