Diversity in the oesophageal phenotypic response to gastro-oesophageal reflux: immunological determinants

RC Fitzgerald, BA Onwuegbusi, M Bajaj-Elliott… - Gut, 2002 - gut.bmj.com
RC Fitzgerald, BA Onwuegbusi, M Bajaj-Elliott, IT Saeed, WR Burnham, MJG Farthing
Gut, 2002gut.bmj.com
Background and aims: Approximately 10% of adults experience gastro-oesophageal reflux
symptoms with a variable oesophageal response. A total of 60% have no endoscopic
abnormality, 30% have oesophagitis, and 10% have Barrett's oesophagus. We investigated
whether the inflammatory cell infiltrate and cytokine profiles of these clinical phenotypes
merely vary in severity or are fundamentally different. Methods: Patients with reflux
symptoms and a normal oesophagus (n= 18), oesophagitis (n= 26), and Barrett's …
Background and aims: Approximately 10% of adults experience gastro-oesophageal reflux symptoms with a variable oesophageal response. A total of 60% have no endoscopic abnormality, 30% have oesophagitis, and 10% have Barrett's oesophagus. We investigated whether the inflammatory cell infiltrate and cytokine profiles of these clinical phenotypes merely vary in severity or are fundamentally different.
Methods: Patients with reflux symptoms and a normal oesophagus (n=18), oesophagitis (n=26), and Barrett's oesophagus (n=22 newly diagnosed, n=28 surveillance) were recruited. Endoscopic and histopathological degrees of inflammation were scored. Cytokine expression was determined by competitive reverse transcriptase-polymerase chain reaction and immunohistochemistry.
Results: In oesophagitis, endoscopic and histopathological grades of inflammation correlated highly. mRNA expression of proinflammatory interleukin (IL)-1β, IL-8, and interferon γ (IFN-γ) were increased 3–10-fold compared with non-inflamed squamous or Barrett's oesophageal samples. There was a modest increase in anti-inflammatory IL-10 but no increase in IL-4. In Barrett's oesophagus, 29/50 had no endoscopic evidence of inflammation and histopathological inflammation was mild in 17/50 and moderate in 24/50, independent of acid suppressants. Expression of IL-1β, IL-8, and IFN-γ was similar to non-inflamed squamous mucosa. IL-10 was increased 1.6-fold similar to oesophagitis. IL-4 was increased fourfold, with 100-fold increase in IL-4/T cell receptor expression, compared with squamous oesophagus or oesophagitis.
Conclusions: Barrett's oesophagus is characterised by a distinct Th-2 predominant cytokine profile compared with the proinflammatory nature of oesophagitis. The specific oesophageal immune responses may influence disease development and progression.
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