Treatment with topical steroids downregulates IL-5, eotaxin-1/CCL11, and eotaxin-3/CCL26 gene expression in eosinophilic esophagitis.
OBJECTIVE
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.
Lucendo
Alfredo J
AJ
Department of Gastroenterology, Hospital Universitario La Paz, Madrid, Spain.
De Rezende
Livia
L
Comas
Carmen
C
Caballero
Teresa
T
Bellón
Teresa
T
D000287:Administration, Topical; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001706:Biopsy; D016022:Case-Control Studies; D054413:Chemokine CCL11 / Q000235:genetics*; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000235:genetics*; D015536:Down-Regulation; D004802:Eosinophilia / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D004941:Esophagitis / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D004947:Esophagus / Q000378:metabolism; D005260:Female; D000068298:Fluticasone; D015870:Gene Expression; D006801:Humans; D015848:Interleukin-5 / Q000235:genetics*; D016014:Linear Models; D018655:Lymphocyte Count; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; C120429:CCL26 protein, human; D054413:Chemokine CCL11; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D015848:Interleukin-5; D000068298:Fluticasone