{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T05:24:24Z","timestamp":1792301064034,"version":"4.4.0"},"reference-count":70,"publisher":"BMJ","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[2002,4]]},"abstract":"<jats:p>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.<\/jats:p>\n               <jats:p>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.<\/jats:p>\n               <jats:p>Results: In oesophagitis, endoscopic and histopathological grades of inflammation correlated highly. mRNA expression of proinflammatory interleukin (IL)-1\u03b2, IL-8, and interferon \u03b3 (IFN-\u03b3) were increased 3\u201310-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-1\u03b2, IL-8, and IFN-\u03b3 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.<\/jats:p>\n               <jats:p>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.<\/jats:p>","DOI":"10.1136\/gut.50.4.451","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T06:30:44Z","timestamp":1027751444000},"page":"451-459","source":"Crossref","is-referenced-by-count":228,"title":["Diversity in the oesophageal phenotypic response to gastro-oesophageal reflux: immunological determinants"],"prefix":"10.1136","volume":"50","author":[{"given":"R C","family":"Fitzgerald","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B A","family":"Onwuegbusi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Bajaj-Elliott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I T","family":"Saeed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W R","family":"Burnham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M J G","family":"Farthing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2002,4,1]]},"reference":[{"key":"2025090711371275000_50.4.451.1","unstructured":"Heartburn across America. Gallup organisation national survey. Princeton, New Jersey: Gallup, 1988."},{"key":"2025090711371275000_50.4.451.2","doi-asserted-by":"crossref","unstructured":"Kaplan-Machlis B, Spiegler G, Revicki D. Health-related quality of life in primary care patients with gastro-oesophageal reflux disease. 1999;33:1032\u20136.","DOI":"10.1345\/aph.18424"},{"key":"2025090711371275000_50.4.451.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199903183401101"},{"key":"2025090711371275000_50.4.451.4","first-page":"2049","volume":"15","year":"1998","journal-title":"Cancer"},{"key":"2025090711371275000_50.4.451.5","doi-asserted-by":"publisher","DOI":"10.3322\/canjclin.48.1.6"},{"key":"2025090711371275000_50.4.451.6","first-page":"933","volume":"63","year":"1997","journal-title":"Am Surg"},{"key":"2025090711371275000_50.4.451.7","first-page":"25","volume":"24","year":"1989","journal-title":"Scand J Gastroenterol"},{"key":"2025090711371275000_50.4.451.8","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/0016-5085(87)90847-X","volume":"92","year":"1987","journal-title":"Gastroenterology"},{"key":"2025090711371275000_50.4.451.9","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)90349-2"},{"key":"2025090711371275000_50.4.451.10","first-page":"A82","volume":"112","year":"1997","journal-title":"Gastroenterology"},{"key":"2025090711371275000_50.4.451.11","doi-asserted-by":"publisher","DOI":"10.1053\/gast.1996.v111.pm8898632"},{"key":"2025090711371275000_50.4.451.12","doi-asserted-by":"publisher","DOI":"10.1136\/gut.37.4.465"},{"key":"2025090711371275000_50.4.451.13","first-page":"333","volume":"24","year":"1998","journal-title":"J Gastrointest Surg"},{"key":"2025090711371275000_50.4.451.14","first-page":"2","volume":"2","year":"1995","journal-title":"Semin Laparosc Surg"},{"key":"2025090711371275000_50.4.451.15","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.1998.00331.x"},{"key":"2025090711371275000_50.4.451.16","doi-asserted-by":"publisher","DOI":"10.1007\/BF02088563"},{"key":"2025090711371275000_50.4.451.17","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1111\/j.1365-2036.1995.tb00405.x","volume":"9","year":"1995","journal-title":"Aliment Pharmacol Ther"},{"key":"2025090711371275000_50.4.451.18","first-page":"32","volume":"92","year":"1997","journal-title":"Am J Gastroenterol"},{"key":"2025090711371275000_50.4.451.19","first-page":"A2584","volume":"118","year":"2000","journal-title":"Gastroenterology"},{"key":"2025090711371275000_50.4.451.20","first-page":"A100","volume":"98","year":"1990","journal-title":"Gastroenterology"},{"key":"2025090711371275000_50.4.451.21","first-page":"1293","volume":"92","year":"1997","journal-title":"Am J Gastroenterol"},{"key":"2025090711371275000_50.4.451.22","first-page":"155","volume":"126","year":"1998","journal-title":"Rev Med Chil"},{"key":"2025090711371275000_50.4.451.23","doi-asserted-by":"publisher","DOI":"10.1126\/science.1925582"},{"key":"2025090711371275000_50.4.451.24","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1998.00532.x"},{"key":"2025090711371275000_50.4.451.25","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.3.389"},{"key":"2025090711371275000_50.4.451.26","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.1999.01372.x"},{"key":"2025090711371275000_50.4.451.27","doi-asserted-by":"publisher","DOI":"10.1038\/35006081"},{"key":"2025090711371275000_50.4.451.28","doi-asserted-by":"crossref","first-page":"147","DOI":"10.3109\/00365529209165436","volume":"27","year":"1992","journal-title":"Scand J Gastroenterol"},{"key":"2025090711371275000_50.4.451.29","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/ijc.2910600103","volume":"60","year":"1995","journal-title":"Int J Cancer"},{"key":"2025090711371275000_50.4.451.30","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5107(87)71676-9"},{"key":"2025090711371275000_50.4.451.31","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.1998.00362.x"},{"key":"2025090711371275000_50.4.451.32","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0016-5085(70)80004-X","volume":"58","year":"1970","journal-title":"Gastroenterology"},{"key":"2025090711371275000_50.4.451.33","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(83)80175-0"},{"key":"2025090711371275000_50.4.451.34","doi-asserted-by":"publisher","DOI":"10.1016\/0046-8177(94)90059-0"},{"key":"2025090711371275000_50.4.451.35","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199610000-00001"},{"key":"2025090711371275000_50.4.451.36","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1016\/S0016-5085(82)80011-5","volume":"83","year":"1982","journal-title":"Gastroenterology"},{"key":"2025090711371275000_50.4.451.37","doi-asserted-by":"publisher","DOI":"10.1007\/BF01215923"},{"key":"2025090711371275000_50.4.451.38","first-page":"G47","volume":"275","year":"1998","journal-title":"Am J Physiol"},{"key":"2025090711371275000_50.4.451.39","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1172\/JCI117676","volume":"95","year":"1995","journal-title":"J Clin Invest"},{"key":"2025090711371275000_50.4.451.40","doi-asserted-by":"crossref","first-page":"5862","DOI":"10.4049\/jimmunol.161.11.5862","volume":"161","year":"1998","journal-title":"J Immunol"},{"key":"2025090711371275000_50.4.451.41","doi-asserted-by":"crossref","unstructured":"Altman D. Practical statistics for medical research. London: Chapman and Hall, 1991.","DOI":"10.1201\/9780429258589"},{"key":"2025090711371275000_50.4.451.42","doi-asserted-by":"publisher","DOI":"10.2307\/2529310"},{"key":"2025090711371275000_50.4.451.43","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1016\/0016-5085(92)91510-B","volume":"103","year":"1992","journal-title":"Gastroenterology"},{"key":"2025090711371275000_50.4.451.44","first-page":"989","volume":"89","year":"1994","journal-title":"Am J Gastroenterol"},{"key":"2025090711371275000_50.4.451.45","first-page":"387","volume":"99","year":"1975","journal-title":"Arch Pathol"},{"key":"2025090711371275000_50.4.451.46","doi-asserted-by":"publisher","DOI":"10.1097\/00005176-199807000-00024"},{"key":"2025090711371275000_50.4.451.47","doi-asserted-by":"publisher","DOI":"10.1097\/00005176-199804000-00004"},{"key":"2025090711371275000_50.4.451.48","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(96)70058-6"},{"key":"2025090711371275000_50.4.451.49","first-page":"1068","volume":"112","year":"1997","journal-title":"Gastroenterology"},{"key":"2025090711371275000_50.4.451.50","doi-asserted-by":"publisher","DOI":"10.1038\/383787a0"},{"key":"2025090711371275000_50.4.451.51","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.3.373"},{"key":"2025090711371275000_50.4.451.52","first-page":"428","volume":"101","year":"1995","journal-title":"Clin Exp Immunol"},{"key":"2025090711371275000_50.4.451.53","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1997.d01-892.x"},{"key":"2025090711371275000_50.4.451.54","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.10.3803"},{"key":"2025090711371275000_50.4.451.55","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.24.9743"},{"key":"2025090711371275000_50.4.451.56","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1182\/blood.V81.1.35.35","volume":"81","year":"1993","journal-title":"Blood"},{"key":"2025090711371275000_50.4.451.57","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90332-8"},{"key":"2025090711371275000_50.4.451.58","doi-asserted-by":"crossref","unstructured":"Kagnoff M, Eckmann L, Yang S, et al. Intestinal epithelial cells: an integral component of the mucosal immune system. In: Kiyono MFK, Kiyono H, eds. Essentials of mucosal immunology. New York: Academic Press, 1996:63\u201371.","DOI":"10.1016\/B978-012394330-9\/50008-9"},{"key":"2025090711371275000_50.4.451.59","unstructured":"Kedlinger M, Freund J, Launay J, et al. Cell interactions through basement membrane in intestinal development and differentiation. In: Sanderson I, Walker W, eds. Development of the gastrointestinal tract. BC Decker Inc, 1999:83\u2013102."},{"key":"2025090711371275000_50.4.451.60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1440-169X.1993.00001.x","volume":"35","year":"1993","journal-title":"Dev Growth Differ"},{"key":"2025090711371275000_50.4.451.61","doi-asserted-by":"crossref","first-page":"6233","DOI":"10.4049\/jimmunol.162.10.6233","volume":"162","year":"1999","journal-title":"J Immunol"},{"key":"2025090711371275000_50.4.451.62","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.4049\/jimmunol.153.5.2122","volume":"153","year":"1994","journal-title":"J Immunol"},{"key":"2025090711371275000_50.4.451.63","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5457.1431"},{"key":"2025090711371275000_50.4.451.64","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81631-1"},{"key":"2025090711371275000_50.4.451.65","doi-asserted-by":"publisher","DOI":"10.1136\/gut.34.12.1649"},{"key":"2025090711371275000_50.4.451.66","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19960915)78:6<1168::AID-CNCR2>3.0.CO;2-6"},{"key":"2025090711371275000_50.4.451.67","first-page":"3620","volume":"57","year":"1999","journal-title":"Cancer Res"},{"key":"2025090711371275000_50.4.451.68","doi-asserted-by":"publisher","DOI":"10.3109\/08830189809043014"},{"key":"2025090711371275000_50.4.451.69","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000171396","volume":"11","year":"1993","journal-title":"Dig Dis"},{"key":"2025090711371275000_50.4.451.70","unstructured":"Poplawski C, Brown R, McCullum R, et al. The failure within the compensatory esophageal mucosal protective mechanisms in patients with Barrett's esophagus as potential contributory factors to the development of mucosal pathology. Gatsroenterology 1998;A3904."}],"container-title":["Gut"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/gut.50.4.451","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T18:37:24Z","timestamp":1757270244000},"score":1,"resource":{"primary":{"URL":"https:\/\/gut.bmj.com\/lookup\/doi\/10.1136\/gut.50.4.451"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,4]]},"references-count":70,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2002,4,1]]},"published-print":{"date-parts":[[2002,4]]}},"alternative-id":["10.1136\/gut.50.4.451"],"URL":"https:\/\/doi.org\/10.1136\/gut.50.4.451","relation":{},"ISSN":["0017-5749","1468-3288"],"issn-type":[{"value":"0017-5749","type":"print"},{"value":"1468-3288","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,4]]}}}