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.

Abstract

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.

• Authors: Jia Yin Yao, Yi Lu, Min Zhi, Chu Jun Li, Pin Jin Hu, Xiang Gao
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 10 Issue 4 Pg. 2105-10 (Oct 2014) ISSN: 1791-3004 [Electronic] Greece
• PMID: 25070376 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Interleukin-17
• Interleukin-23
• Nuclear Receptor Subfamily 1, Group F, Member 3
• RNA, Messenger
• Trinitrobenzenesulfonic Acid

Topics

• Animals
• Antibodies, Monoclonal (immunology, therapeutic use)
• Crohn Disease (chemically induced, drug therapy, pathology)
• Disease Models, Animal
• Interleukin-17 (blood, genetics, metabolism)
• Interleukin-23 (blood, genetics, metabolism)
• Male
• Nuclear Receptor Subfamily 1, Group F, Member 3 (blood, genetics, metabolism)
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Severity of Illness Index
• Trinitrobenzenesulfonic Acid (toxicity)