Proinflammatory cytokines alter/reduce esophageal circular muscle contraction in experimental cat esophagitis

• Published in: American journal of physiology: Gastrointestinal and liver physiology 2004-12, Vol.50 (6), p.G1131-G1139
• Main Authors: WEIBIAO CAO, LING CHENG, BEHAR, José, FIOCCHI, Claudio, BIANCANI, Piero, HARNETT, Karen M
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cats; Cytokines; Esophagus; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Medical sciences; Muscular system; Other diseases. Semiology; Throat; Vertebrates: digestive system
• ISSN: 0193-1857; 1522-1547

Cholinergic mechanisms are largely responsible for esophageal contraction in response to swallowing or to in vitro electrical field stimulation (EFS). After induction of experimental esophagitis by repeated acid perfusion, the responses to swallowing and to EFS were significantly reduced but contraction in response to ACh was not affected, suggesting that cholinergic mechanisms are damaged by acid perfusion but that myogenic mechanisms are not. Measurements of ACh release in response to EFS confirmed that release of ACh was reduced in esophagitis compared with normal controls. To examine factors contributing to this neuropathy, normal esophageal strips were incubated for 1-2 h with the proinflammatory cytokines IL-1beta (100 U/ml), IL-6 (1 ng/ml), or TNF-alpha (1 ng/ml). IL-1beta and IL-6 levels, measured by Western blot analysis, increased in esophagitis compared with normal circular muscle. IL-1beta and IL-6 reduced contraction in response to EFS (2-10 Hz, 0.2 ms) but did not affect ACh-induced contraction, suggesting that these cytokines inhibit ACh release without affecting myogenic contractile mechanisms. EFS-induced ACh release was significantly reduced in normal esophageal strips by incubation in IL-1beta or IL-6, suggesting that they may contribute to the contractility changes. TNF-alpha at 1 ng/ml, however, did not affect the response to ACh or to electrical stimulation but inhibited both at higher concentrations. TNF-alpha levels were low in normal muscle and did not increase with esophagitis. The data suggest that the proinflammatory cytokines IL-1beta and IL-6 contribute to reduced esophageal contraction by inhibiting release of ACh from myenteric neurons. [PUBLICATION ABSTRACT]