Inhibition of cytokines and ICAM-1 induction in rheumatoid fibroblasts by anti-NF-kappa B reagents

The role of the transcription factor, nuclear factor NF-kappa B, in the induction of cytokines and intercellular adhesion molecule-1 (ICAM-1) on stimulation with interleukin-l (IL-1) and tumor necrosis factor-alpha. (TNF-alpha) was studied in primary rheumatoid synovial fibroblasts (RSF) obtained from patients with rheumatoid arthritis (RA). The production of GM-CSF, IL-6, and IL-8 and the expression of ICAM-1 were augmented after nuclear translocation of NF-kappa B induced by treatment with IL-1 or TNF-alpha. We examined the effects of N-acetyl-L-cysteine (NAC) and acetylsalicylic acid (aspirin) on the induction of proinflammatory cytokines and ICAM-1. Pretreatment of RSF with NAC inhibited nuclear translocation of NF-kappa B completely, and the induction of these cytokines and ICAM-1 was markedly suppressed. On the other hand, the effect of aspirin was only partial. These observations indicate the pivotal role of NF-kappa B in RA pathogenesis, thus highlighting the possibility of a novel therapeutic strategy.