Comparison of anti-inflammatory and anti-angiogenic effects of JAK inhibitors in IL-6 and TNFα-stimulated fibroblast-like synoviocytes derived from patients with RA

Abstract

Abstract Rheumatoid arthritis (RA) involves synovial tissue proliferation, inflammation, and angiogenesis, and contributes to joint destruction. Angiogenesis is a key therapeutic target for the treatment of RA, and Janus kinase (JAK) inhibitors have emerged as a promising therapy. In this study, we compared the inhibitory effects of five JAK inhibitors, including tofacitinib (TOF), baricitinib, peficitinib, upadacitinib, and filgotinib, on interleukin (IL)-6-induced inflammation in RA synovial tissues. All five inhibitors effectively suppressed IL-6-induced inflammatory and angiogenic factors, including vascular endothelial growth factor, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, by inhibiting the phosphorylation of signal transducer and activator of transcription (STAT)1 and STAT3. Overall, the results suggest that while all five JAK inhibitors are effective in reducing IL-6-induced inflammatory and angiogenic factors, their efficacy may differ owing to specific molecular mechanisms and pharmacological properties.

Keywords

• Rheumatoid arthritis
• JAK inhibitors
• STAT
• IL-6
• TNF-alpha