Role of Th-2 cytokines in the development of Barrett's esophagus in rats

Barrett's esophagus is characterized by a distinct Th-2-predominant cytokine profile, unlike the pro-inflammatory nature of reflux esophagitis. The aim of this study was to examine the role of Th-2 cytokines during the development of Barrett's esophagus, using a rat model. Barrett's esophagus was induced by Levrat's esophagojejunostomy technique in Brown-Norway (BN) rats. Rats were killed at 8, 15, 30, and 50 weeks after the operation. We studied the incidences of esophagitis and Barrett's esophagus, and the mRNA expression of cytokines and CDX2 by real-time reverse transcriptase-polymerase chain reaction and immunohistochemical staining. Finally, we compared the incidence of Barrett's esophagus in BN rats with that in Sprague-Dawley (SD) rats. Esophagitis was found in all rats. Barrett's esophagus appeared 8 weeks after the operation, and its incidence and length increased over time. Levels of Th-2 cytokines such as interleukin (IL)-4, IL-10, and IL-13 were significantly increased in Barrett's esophagus as compared to those in non-Barrett's esophagus, while there were no differences in the levels of pro-inflammatory cytokines. The peak of elevated IL-4 mRNA was observed before that of CDX2 mRNA. IL-4 was co-localized in CD4-positive cells and CDX2-positive goblet cells. The incidence of Barrett's esophagus was more common in BN rats (8/10, 80%) than in SD rats (2/7, 28%) at 30 weeks. Th-2 cytokines, especially IL-4, may play a crucial role in the development of Barrett's esophagus in an early phase. These results provide understanding of the pathogenesis of Barrett's esophagus from the aspect of the Th-2 immune response.