Inhibition of the interleukin-23/interleukin-17 pathway by anti-interleukin-23p19 monoclonal antibody attenuates 2,4,6-trinitrobenzene sulfonic acid-induced Crohn's disease in rats.

The interleukin (IL)-23/IL-17 pathway is considered to be important in the pathogenesis of Crohn's disease (CD). The present study aimed to evaluate the effects of targeting the IL-23/IL-17 pathway using the anti-IL-23p19 monoclonal antibody (mAb) on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD rats. A total of 60 Sprague-Dawley rats were randomly divided into a control group, model group and an anti-IL-23p19 mAb treatment group (administered intramuscularly every week at a dose of 1 ml/mg). Disease activity index (DAI), colon macroscopic damage index (CMDI) and tissue damage index (TDI) were then evaluated. The mRNA expression of IL-23p19, p40 (IL-23/12), retinoic acid-related orphan receptor-γt (ROR-γt) and IL-17 in colonic tissues were detected by reverse transcription-polymerase chain reaction and levels of serum IL-23p19, p40, ROR-γt and IL-17 were measured using an enzyme-linked immunosorbent assay. Anti-IL-23p19 mAb was found to effectively attenuate colonic inflammation demonstrated by reduced DAI, CMDI and TDI scores, improvement in pathological evaluation and downregulation of expression levels of IL-23p19, p40 (IL-23/12), ROR-γt and the downstream proinflammatory cytokine, IL-17. Anti-IL-23p19 mAb attenuated TNBS-induced CD in model rats. The possible underlying mechanisms may be associated with inhibition of the IL-23/IL-17 pathway by inhibiting the expression of IL-23p19 and downregulating the downstream proinflammatory cytokine IL-17. Targeting the IL-23/IL-17 pathway may be a relevant and realistic therapeutic approach for the development of additive and alternative treatments to the biologics currently available in the treatment of CD. [ABSTRACT FROM AUTHOR]