The IL-23/IL-17/NF-κB Signaling Pathway in Rheumatoid Arthritis: Molecular Mechanisms and Therapeutic Agents

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation of the joint synovium, which can lead to bone destruction. Prolonged inadequate treatment can result in joint disability and an increased risk of mortality. Currently, there are considerable limitations in the availability of effective therapeutic agents for RA. The IL-23/IL-17/NF-κB signaling pathway has emerged as a central pathogenic mechanism underlying the multistage development of RA. This pathway initiates the initial inflammatory response, driving excessive proliferation of the synovial tissue, ultimately leading to late-stage bone and cartilage destruction. A comprehensive understanding of the role of the IL-23/IL-17/NF-κB pathway in the pathogenesis of RA can facilitate the refinement of scientific understanding of RA pathogenesis and assist in developing new therapeutic regimens. A comprehensive literature review and data search were conducted in several scientific databases, including Web of Science, PubMed, Google Scholar, Embase, TCMSP, PubChem, Swiss ADME, and Swiss Target Prediction. The literature review was conducted from 2013 to 2025. The search terms employed included RA, IL-23, IL-17, NF-κB, molecular mechanisms, and therapeutic agents. Following a rigorous screening process, irrelevant data were excluded, resulting in a focused analysis and comprehensive review of the key role of the IL-23/IL-17/NF-κB signaling axis in the multifaceted pathogenesis of RA and the key active ingredients and possible targets of action of related drugs. This comprehensive literature review aims to provide novel mechanistic insights and valuable references to guide the development of more effective therapeutic strategies for this debilitating autoimmune disease.