Gastroesophageal reflux disease-associated esophagitis induces endogenous cytokine production leading to motor abnormalities.
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.
Rieder
Florian
F
Division of Gastroenterology, University Hospitals of Cleveland, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Cheng
Ling
L
Harnett
Karen M
KM
Chak
Amitabh
A
Cooper
Gregory S
GS
Isenberg
Gerard
G
Ray
Monica
M
Katz
Jeffry A
JA
Catanzaro
Andrew
A
O'Shea
Robert
R
Post
Anthony B
AB
Wong
Richard
R
Sivak
Michael V
MV
McCormick
Thomas
T
Phillips
Manijeh
M
West
Gail A
GA
Willis
Joseph E
JE
Biancani
Piero
P
Fiocchi
Claudio
C
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
D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger