Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by
persistent joint swelling and progressive destruction of cartilage and bone.
Current RA treatments are largely empirical in origin and their precise
mechanism of action is uncertain. Increasing evidence shows that chronic
inflammatory diseases such as RA are caused by prolonged production of
proinflammatory cytokines including tumor necrosis factor (TNF) and interleukin
1 (IL-1). The nuclear factor κB (NF-κB) plays an essential role in
transcriptional activation of TNF and IL-1. NF-κB is induced by many stimuli
including TNF and IL-1, forming a positive regulatory cycle that may amplify and
maintain RA disease process. NF-κB and enzymes involved in its activation
can be a target for anti-inflammatory treatment. Aspirin and sodium salicylate
inhibit activation of NF-κB by blocking IκB kinase, a key enzyme in
NF-κB activation. Glucocorticoids suppress expression of inflammatory genes
by binding glucocorticoid receptor with NF-κB, and increasing expression of
inhibitory protein of NF-κB, IκBα. Sulfasalazine and gold compounds
also inhibit NF-κB activation. Continuing advances in our understanding of
action mechanism of antirheumatic agents will benefit the future development of
RA regimens with greater efficacy and less toxicity.