Extracellular HMGB1 may play a major role in the pathogenesis of synovitis, since it is a potent promotor of macrophage activation including induction of TNF as well as IL-1 synthesis and other pro-inflammatory mediators [13-15]; Extracellular HMGB1 is abundantly expressed in serum, in synovitis and in intra-articular fluid of patients with rheumatoid arthritis as well as in experimental arthritis [16-18]. This evidence concerns the gene TNF and synovitis.