title: Subepithelial collagen deposition, profibrogenic cytokine gene expression, and changes after prolonged fluticasone propionate treatment in adult eosinophilic esophagitis: a prospective study.
abstract: BACKGROUND
  Recent research shows that both pediatric and adult patients with eosinophilic esophagitis (EoE) experience esophageal remodeling marked by increased collagen deposition in which TGF-β plays an important role. However, limited data are available on the intensity and reversibility of fibrous remodeling in adults with EoE.
  
  
  OBJECTIVE
  We sought to analyze differences in collagen deposition in the lamina propria (LP) and profibrogenic cytokine gene expression along with other changes induced by prolonged treatment with fluticasone propionate in adults with EoE.
  
  
  METHODS
  Ten adults given consecutive diagnoses of EoE were studied prospectively. Deep esophageal biopsy specimens were obtained before and after 1 year of treatment with fluticasone propionate. Collagen deposition in the LP was assessed in tissue sections with the aid of the Masson trichrome technique. IL5, TGFB1, fibroblast growth factor 9 (FGF9), and CCL18 gene expression was quantified through real-time PCR. EoE results were compared among samples from 10 adult patients with gastroesophageal reflux disease and 10 control subjects with healthy esophagi.
  
  
  RESULTS
  Patients with EoE showed a significant increase in subepithelial collagen deposition; this correlated positively with eosinophil density in the LP and the patient's age. Prolonged steroid treatment induced a nonsignificant reduction in subepithelial fibrosis, which remained significantly higher than in control subjects. Profibrogenic cytokine gene expression also increased in patients with EoE, with IL5 (P < .001), FGF9 (P = .005), and CCL18 (P = .008) all significantly upregulated. After 1 year of treatment, a reduction was observed in gene expression; for CCL18 expression, this decrease was statistically significant (P < .001).
  
  
  CONCLUSIONS
  Esophageal remodeling is associated with upregulated gene expression of profibrogenic cytokines in adults with EoE. Prolonged treatment with fluticasone propionate leads to a nonsignificant reduction in subepithelial collagen deposition accompanied by downregulation of profibrogenic cytokine gene expression, with that of CCL18 being especially significant.
authors: Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Spain. alucendo@vodafone.es
authors: Alfredo J
authors: AJ
authors: Lucendo
authors: Angel
authors: A
authors: Arias
authors: Livia C
authors: LC
authors: De Rezende
authors: Jose Luis
authors: JL
authors: Yagüe-Compadre
authors: Teresa
authors: T
authors: Mota-Huertas
authors: Sonia
authors: S
authors: González-Castillo
authors: Rubén A
authors: RA
authors: Cuesta
authors: José M
authors: JM
authors: Tenias
authors: Teresa
authors: T
authors: Bellón
mesh_terms: D000293:Adolescent; D000328:Adult; D000730:Androstadienes / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003094:Collagen / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D057765:Eosinophilic Esophagitis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D005260:Female; D005355:Fibrosis / Q000188:drug therapy / Q000473:pathology; D000068298:Fluticasone; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D003094:Collagen; D000068298:Fluticasone