Basic—Alimentary TractGastroesophageal Reflux Might Cause Esophagitis Through a Cytokine-Mediated Mechanism Rather Than Caustic Acid Injury
Section snippets
Rat model of reflux esophagitis (esophagoduodenostomy)
This study was approved by the animal care committee of the Dallas VA Medical Center. Six-week-old male Sprague–Dawley rats (Charles River Laboratories, Wilmington, MA) were housed 2 per cage under standard laboratory conditions.
Esophagoduodenostomy was performed in 34 animals using a modification of the esophagojejunostomy technique described by Buttar et al.11 This surgery left the vagally innervated stomach in place so that both gastric and duodenal contents could reflux into the esophagus.
Time course and distribution of tissue inflammation in the distal esophagus
In the sham-operated control animals, no inflammation was observed in any tissue layer of the distal esophagus (Figure 1). In animals that had an esophagoduodenostomy, in contrast, esophageal inflammation was observed at day 3, which was most prominent in the submucosa (Figure 2). Inflammation increased to first reach significantly increased levels in the lamina propria by week 1 and in the epithelial layer by week 3 (Figure 2). From weeks 3 to 8, the overall degree of inflammation remained
Discussion
The development of reflux esophagitis that we have observed in our systematic histologic study of the rat esophagus after esophagoduodenostomy is not consistent with the prevailing concept of reflux esophagitis as a caustic chemical injury. An esophageal injury caused by the direct toxic effects of refluxed gastric acid would be expected to start with the death of surface epithelial cells, which would evoke an acute inflammatory response with epithelial infiltration by polymorphonuclear cells.
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2022, Journal of EthnopharmacologyCitation Excerpt :A clinical study of the RE pathogenesis explored the hypothesis that the development of RE is cytokine-mediated injury rather than acid burn (Dunbar et al., 2016). Refluxed gastric juice stimulated esophageal epithelial cells to secrete cytokines that induce epithelial proliferative changes, attract the T lymphocytes and other inflammatory cells that eventually destroy the mucosa instead of killing esophageal epithelial cells directly (Souza et al., 2009). Overdosed and continuous gastroesophageal reflux may activate inflammatory pathways, trigger more release of cytokines and chemokines from injured cells and impair mucosal barrier function (Orlando, 2010; Woodland et al., 2013).
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Conflicts of interest The authors disclose no conflicts.
Funding Supported by the Office of Medical Research, Department of Veterans Affairs (R.F.S. and S.J.S.), and the National Institutes of Health (DK63621 to R.F.S. and CA134571 to R.F.S. and S.J.S.).