Neutralizing IL-23 is superior to blocking IL-17 in suppressing intestinal inflammation in a spontaneous murine colitis model

Abstract

Background: IL-23/T H 17 inflammatory responses are regarded as central to the pathogenesis of inflammatory bowel disease, but clinically IL-17A antibodies have shown low efficacy and increased infections in Crohn's disease. Hence, we decided to closely examine the role of the IL-23/T H 17 axis in 3 models of colitis. Methods: IL-17A -/- and IL-17Ra -/- T cells were transferred into Rag1 -/- and RaW mice to assess the role of IL-17A-IL-17Ra signaling in T cells during colitis. In Winnie mice with spontaneous colitis due to an epithelial defect, we studied the progression of colitis in the absence of IL-17A and the efficacy of neutralizing antibodies against the IL-17A or IL-23p19 cytokines. ..