Pathogenesis And Treatment Of Rheumatoid Arthritis Based On Inflammation

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovitis and joint destruction. Its pathogenesis involves complex interactions between genetic, environmental and immune system factors. In recent years, JAK/STAT and NF-κB signaling pathways have become the focus of research due to their central role in pro-inflammatory factor expression and immune cell activation. The continuous activation of JAK/STAT pathway can further aggravate inflammation and bone destruction by inhibiting apoptosis of synovial fibroblasts, promoting differentiation of Th17 cells and activating osteoclasts, while NF-κB pathway can regulate the expression of inflammatory factors such as IL-6 and IL-8 through classical and non-classical pathways, forming an amplified inflammatory network. Cross-regulation accelerates RA pathologies. In terms of therapeutic strategy, JAK inhibitors effectively reduce disease activity by blocking STAT phosphorylation, while a new generation of selective JAK3 inhibitors aims to reduce the risk of side effects. Against the NF-κB pathway, synthetic inhibitors such as BMS-345541 and natural compounds such as curcumin exert anti-inflammatory effects by inhibiting IKKβ activity or promoting IκBα degradation. Combination therapy has shown superior efficacy by synergizing inhibition of inflammatory response through multiple pathways. However, resistance and long-term safety issues still need to be overcome. Future research needs to integrate multi-omics data with artificial intelligence models to shift from "pathway inhibition" to "immune homeostasis reconstruction" to develop more precise and safe treatment strategies to improve the prognosis and quality of life of RA patients.