HMGB1 and rheumatoid arthritis: At present, ironclad evidence that HMGB1 is an important mediator of disease in humans is still lacking, although elevated circulating levels of HMGB1 have been detected in patients with sepsis [12], ARDS [13] or rheumatoid arthritis [14] and high levels of HMGB1 have been found in samples of synovial fluid from patients with rheumatoid arthritis [15].