Treatment with topical steroids downregulates IL-5, eotaxin-1/CCL11, and eotaxin-3/CCL26 gene expression in eosinophilic esophagitis

Am J Gastroenterol. 2008 Sep;103(9):2184-93. doi: 10.1111/j.1572-0241.2008.01937.x.

Abstract

Objectives: Our aim was to evaluate the changes induced by topical steroid treatment to the esophageal epithelial inflammatory eosinophilic and T-cell infiltrate and to IL-5, eotaxin-1/CCL11, and eotaxin-3/CCL26 esophageal gene expression levels in patients with eosinophilic esophagitis (EE).

Methods: Esophageal biopsies were taken from eight adult patients at the moment of diagnosis and after 3-month treatment with fluticasone propionate. Eosinophils, CD8, and CD4 T cells were examined by immunohistochemistry. IL-5, eotaxin-1/CCL11, and eotaxin-3/CCL26 gene expression levels were measured by real-time PCR. Eight control samples were also analyzed.

Results: A significant decrease in the eosinophil infiltrate and in CD8(+) T-cell density was observed in the esophageal epithelium from the patients upon steroid treatment. IL-5 was not detected in control samples, and expression levels were variably downregulated after treatment in six of the patients. Gene expression of eotaxin-1/CCL11 showed relevant downregulation in four cases and a modest twofold decrease in three of the patients studied. Mean CCL11 expression values upon steroid treatment were similar to control samples (19.4 +/- 28.6 vs 8.42 +/- 5, P= 0.7). Eotaxin-3/CCL26 gene expression levels were significantly increased in EE. Although they were significantly downregulated upon steroid treatment, control expression levels were not reached in any of the cases analyzed (580.9 +/- 943.9 vs 1.45 +/- 1.0, P= 0.001).

Conclusions: Our results confirm that eotaxin-3/CCL26 is significantly increased in EE esophageal samples. However, the individual analysis of IL-5, CCL11, and CCL26 expression data suggests that several cytokines and chemokines could participate in the physiopathology of EE in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Adult
  • Androstadienes / administration & dosage*
  • Anti-Inflammatory Agents / administration & dosage*
  • Biopsy
  • Case-Control Studies
  • Chemokine CCL11 / genetics*
  • Chemokine CCL26
  • Chemokines, CC / genetics*
  • Down-Regulation
  • Eosinophilia / drug therapy*
  • Eosinophilia / genetics*
  • Eosinophilia / immunology
  • Esophagitis / drug therapy*
  • Esophagitis / genetics*
  • Esophagitis / immunology
  • Esophagus / metabolism
  • Female
  • Fluticasone
  • Gene Expression*
  • Humans
  • Interleukin-5 / genetics*
  • Linear Models
  • Lymphocyte Count
  • Male
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Androstadienes
  • Anti-Inflammatory Agents
  • CCL26 protein, human
  • Chemokine CCL11
  • Chemokine CCL26
  • Chemokines, CC
  • Interleukin-5
  • Fluticasone