Published online Sep 16, 2022. doi: 10.12998/wjcc.v10.i26.9254
Peer-review started: March 16, 2022
First decision: April 10, 2022
Revised: April 21, 2022
Accepted: August 12, 2022
Article in press: August 12, 2022
Published online: September 16, 2022
Gastroesophageal reflux disease (GERD) has a number of manifestations, including erosive esophagitis (EE) and non-erosive form of GERD (NERD). Similar levels of intraesophageal acidity are often found in subjects with EE and NERD and little is known about the reasons.
Several reports suggest involvement of inflammatory cytokines in the pathogenesis of different forms of GERD. Local inflammatory response of the esophageal mucosa to gastroesophageal reflux (GER) may depend on gene expression of cytokines. However, data on the dependence of the expression on esophageal acidity are still lacking.
The objective of the study was to explore gene expression of inflammatory cytokines in esophageal mucosa in patients with EE and NERD and its association with data of esophageal multichannel intraluminal impedance-pH measurements.
The data were obtained in a single-center prospective study. We analyzed the expression of interleukin (IL)-1β, IL-10, IL-18, tumor necrosis factor α (TNFA), toll-like receptor 4 (TLR4), GATA binding protein 3 (GATA3), differentiation cluster 68 (CD68), and β-2 microglobulin genes in esophageal mucosa samples obtained during endoscopy. All the subjects underwent multichannel intraluminal impedance-pH measurements. Based on the presence of abnormal results, they were allocated either to the GERD group or to the control group. The GERD group was further divided into the EE group and the NERD group. Spearman’s rank correlation analysis was used to analyze association of cytokine expression with esophageal acidity and number and types of GER.
We found higher expression of IL-18 and GATA3 genes in the EE group compared to the NERD group. Expression of IL-1β, IL-18, TNFA, and TLR4 was lower (P < 0.05) in the control group compared to EE and NERD. Esophageal acid exposure correlated with the expression of IL-1β (Spearman’s rank r = 0.29), IL-18 (r = 0.31), TNFA (r = 0.35), GATA3 (r = 0.34), and TLR4 (r = 0.29), CD68 (r = 0.37). Mean esophageal pH correlated inversely with the expression of IL-18, TNFA, GATA3, TLR4, and CD68. No association of the gene expression with number of GER was found.
In patients with EE, local expression of IL-18 and GATA3 was higher compared to subjects with NERD. Esophageal acid exposure correlated directly with expression of IL-1β, IL-18, TNFA, TLR4, CD68, and β-2 microglobulin. An inverse correlation was revealed between the expression of IL-18, TNFA, GATA3, TLR4, and CD68 and mean esophageal acidity. Expression levels of IL-10 did not differ significantly in the studied groups and did not correlate with esophageal acid exposure and number of GER.
Larger studies are necessary to confirm the obtained results. Assessment of the association of the local inflammatory response with concentration of bile acids within the refluxate seems promising.