The ligands for complex formation with HMGB1 in this study, IL-1α, IL-1β and LPS, were chosen for three reasons; I) we and others have previously demonstrated a cytokine-enhancing effect of such complexes in macrophages [16,17,48]; II) HMGB1 [23], LPS [42], IL-1α and IL-1β [38-40] have all been detected in RA and OA synovial samples; and III) fibroblasts are pivotal cells in arthritic inflammation that express the suggested receptors for HMGB1 [23,35,49-51] in addition to the LPS receptor TLR4 and IL-1RI [34-37]. Here, TLR4 is linked to rheumatoid arthritis.