Cytokines and immune modulators—Effects on esophageal inflammation

Traditionally, reflux esophagitis has been assumed to develop as a caustic chemical injury whereby esophageal squamous cells succumb to damage inflicted by an “acid burn.” According to this concept, death of surface cells incites a granulocytic inflammatory response that starts at the surface with progression into the lamina propria and stimulates a proliferative response leading to basal cell hyperplasia. However, more recent studies in rats and humans have demonstrated an immune-mediated response initiated by the secretion of inflammatory cytokines by reflux-exposed squamous cells, which attract T lymphocytes to the submucosa with subsequent progression to the luminal surface, followed by basal cell hyperplasia, and finally surface cell death. This chapter will review the esophageal mucosal defense systems, the role of cytokines as initiators of acute reflux esophagus, as well as the contribution of the innate and adaptive immune systems to reflux-induced esophageal inflammation.