title: Gastroesophageal reflux disease-associated esophagitis induces endogenous cytokine production leading to motor abnormalities.
abstract: OBJECTIVE
  Gastroesophageal reflux disease is a condition frequently associated with esophagitis and motor abnormalities. Recent evidence suggests that proinflammatory cytokines, such as interleukin (IL)-1beta and IL-6, may be implicated because they reduce esophageal muscle contractility, but these results derive from in vitro or animal models of esophagitis. This study used human esophageal cells and tissues to identify the cellular source of cytokines in human esophagitis investigate whether cytokines can be induced by gastric refluxate, and examine whether esophageal tissue- or cell-derived mediators affect muscle contractility.
  
  
  METHODS
  Endoscopic mucosal biopsy specimens were obtained from patients with and without esophagitis, organ-cultured, and undernatants were assessed for cytokine content. The cytokine profile of esophageal epithelial, fibroblast, and muscle cells was analyzed, and esophageal mucosa and cell products were tested in an esophageal circular muscle contraction assay.
  
  
  RESULTS
  The mucosa of esophagitis patients produced significantly greater amounts of IL-1beta and IL-6 compared with those of control patients. Cultured esophageal epithelial cells produced IL-6, as did fibroblasts and muscle cells. Epithelial cells exposed to buffered, but not denatured, gastric juice produced IL-6. Undernatants of mucosal biopsy cultures from esophagitis patients reduced esophageal muscle contraction, as did supernatants from esophageal epithelial cell cultures.
  
  
  CONCLUSIONS
  The human esophagus produces cytokines capable of reducing contractility of esophageal muscle cells. Exposure to gastric juice is sufficient to stimulate esophageal epithelial cells to produce IL-6, a cytokine able to alter esophageal contractility. These results indicate that classic cytokines are important mediators of the motor disturbances associated with human esophageal inflammation.
authors.affiliation: Division of Gastroenterology, University Hospitals of Cleveland, Case Western Reserve University School of Medicine, Cleveland, Ohio.
authors.forename: Florian
authors.initials: F
authors.lastname: Rieder
authors.forename: Ling
authors.initials: L
authors.lastname: Cheng
authors.forename: Karen M
authors.initials: KM
authors.lastname: Harnett
authors.forename: Amitabh
authors.initials: A
authors.lastname: Chak
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Cooper
authors.forename: Gerard
authors.initials: G
authors.lastname: Isenberg
authors.forename: Monica
authors.initials: M
authors.lastname: Ray
authors.forename: Jeffry A
authors.initials: JA
authors.lastname: Katz
authors.forename: Andrew
authors.initials: A
authors.lastname: Catanzaro
authors.forename: Robert
authors.initials: R
authors.lastname: O'Shea
authors.forename: Anthony B
authors.initials: AB
authors.lastname: Post
authors.forename: Richard
authors.initials: R
authors.lastname: Wong
authors.forename: Michael V
authors.initials: MV
authors.lastname: Sivak
authors.forename: Thomas
authors.initials: T
authors.lastname: McCormick
authors.forename: Manijeh
authors.initials: M
authors.lastname: Phillips
authors.forename: Gail A
authors.initials: GA
authors.lastname: West
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Willis
authors.forename: Piero
authors.initials: P
authors.lastname: Biancani
authors.forename: Claudio
authors.initials: C
authors.lastname: Fiocchi
mesh_terms: D000818:Animals; D001706:Biopsy; D002415:Cats; D002460:Cell Line; D015154:Esophageal Motility Disorders / Q000276:immunology* / Q000473:pathology*; D004941:Esophagitis / Q000276:immunology / Q000473:pathology; D004947:Esophagus / Q000166:cytology; D005750:Gastric Juice; D005764:Gastroesophageal Reflux / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D009092:Mucous Membrane / Q000276:immunology / Q000473:pathology; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000502:physiology; D009924:Organ Culture Techniques; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger