Adult-onset Still’s disease (AOSD) is an obscure disease that is usually diagnosed after the exclusion of other febrile diseases, including other autoimmune, infectious, and malignant diseases. Although definitive diagnostic criteria and treatment guidelines for AOSD are thus far lacking, the typical manifestations of AOSD have been identified and effective medications for remission and maintenance have been proposed. The pathophysiology of the AOSD is unclear, but diagnostic criteria and treatment guidelines for AOSD can be established by determining its core etiology and conducting clinical trials of previously tested immunosuppressants and biologics.

Objective: The aim of this study was to clarify whether stimulation of recombinant TLR2 and TLR4 by their specific ligands induces the production of RANKL and IL-6 in the fibroblast-like synoviocytes (FLSs) from RA patients.Methods: FLSs were isolated from RA synovial tissues and they were stimulated with the IL-17, TLR2 ligand bacterial peptidoglycan (PGN) and TLR4 ligand lipopolysaccharide (LPS). The RANKL levels were assessed by RT-PCR and western blotting. The expressions of IL-17, TLR2, TLR4, RANKL and IL-6 in the RA synovium were quantified by immunohistochemistry and these values were compared with the values obtained in the osteoarthritis synovium. The increased IL-6 production in the culture supernatants of the RA FLSs was quantified by sandwich ELISA. Results:The mRNA and protein levels of RANKL and IL-6 increased in the RA FLSs stimulated with PGN, LPS and IL-17, or PGN plus IL-17 or LPS plus IL-17. The expressions