Interleukin-13 Mediates Non-Steroidal Anti-Inflammatory-Drug-Induced Small Intestinal Mucosal Injury with Ulceration

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs), which are antipyretics and analgesics, cause gastrointestinal disorders, such as inflammation and ulcers. To prescribe NSAIDs more safely, it is important to clarify the mechanism of NSAID-induced gastrointestinal mucosal injury. However, there is a paucity of studies on small intestinal mucosal damage by NSAIDs, and it is currently unknown whether inflammation and ulceration also occur in the small intestine, and whether mediators are involved in the mechanism of injury. Therefore, in this study, we created an animal model in which small intestinal mucosal injury was induced using NSAIDs (indomethacin; IDM). Focusing on the dynamics of immune regulatory factors related to the injury, we aimed to elucidate the pathophysiological mechanism involved. We analyzed the pathological changes in the small intestine, the expression of immunoregulatory factors (cytokines), and identified cytokine secretion and expression cells from isolated lamina propria mononuclear cells (LPMCs). Ulcers were formed in the small intestine by administering IDM. Although the mRNA expression levels of IL-1β, IL-6, and TNFα were decreased on day 7 after IDM administration, IL-13 mRNA levels increased from day 3 after IDM administration and remained high even on day 7. The IL-13 mRNA expression and the secretion of IL-13 were increased in small intestinal LPMCs isolated from the IDM-treated group. In addition, we confirmed that IL-13 was expressed in CD4-positive T cells. These results provided new evidence that IL-13 production from CD4-positive T cells in the lamina propria of the small intestine contributes to NSAID-induced mucosal injury.