NF-kappa B in rheumatoid arthritis: a pivotal regulator of inflammation, hyperplasia, and tissue destruction

The transcription factor NF-kappaB has been well recognized as a pivotal re gulator of inflammation in rheumatoid arthritis (RA), but recent developmen ts revealed a broad involvement of NF-kappaB in other aspects of RA patholo gy, including development of T helper 1 responses, activation, abnormal apo ptosis and proliferation of RA fibroblast-like synovial cells, and differen tiation and activation of bone resorbing activity of osteoclasts. In agreem ent with this, studies in animal models of RA have demonstrated the high th erapeutic efficacy of specific inhibitors of NF-kappaB pathway, indicating the feasibility of anti-NF-kappaB therapy for human disease.