Diversity in the oesophageal phenotypic response to gastro-oesophageal reflux: immunological determinants.
OBJECTIVE
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)-1beta, IL-8, and interferon gamma (IFN-gamma) 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-1beta, IL-8, and IFN-gamma 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.
Fitzgerald
R C
RC
Cancer Cell Unit, Hutchison-MRC Research Centre, Hills Road, Cambridge CB2 2XZ, UK. rcf@hutchison-mrc.cam.ac.uk
Onwuegbusi
B A
BA
Bajaj-Elliott
M
M
Saeed
I T
IT
Burnham
W R
WR
Farthing
M J G
MJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D004941:Esophagitis / Q000276:immunology*; D005260:Female; D005764:Gastroesophageal Reflux / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines; D012333:RNA, Messenger