TY - JOUR T1 - The Tumor Necrosis Factor-α-blocking Agent Infliximab Inhibits Interleukin 1β (IL-1β) and IL-6 Gene Expression in Human Osteoblastic Cells JF - The Journal of Rheumatology JO - J Rheumatol DO - 10.3899/jrheum.081321 SP - jrheum.081321 AU - Estella Musacchio AU - Chiara Valvason AU - Constantin Botsios AU - Francesca Ostuni AU - Antonio Furlan AU - Roberta Ramonda AU - Valentina Modesti AU - Leonardo Sartori AU - Leonardo Punzi Y1 - 2009/06/30 UR - http://www.jrheum.org/content/early/2009/06/27/jrheum.081321.abstract N2 - Objective Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine involved in the pathogenesis of several rheumatic diseases, including rheumatoid arthritis (RA), associated with systemic bone loss and subchondral bone erosions. TNF-α-blocking agents such as infliximab have been successful in treatment of disease-modifying antirheumatic drug-resistant rheumatic diseases. Infliximab therapy in RAalso had beneficial effects on local bone destruction and bone mineral density. We assessed effects of infliximab treatment on the bone tissue compartment and cytokine profile expression in vitro. Methods Osteoblast-like cells were exposed for 24 h to sera of RA patients collected at baseline and after 1 month (T1) and 3 years (T2) of infliximab treatment. Total RNA was extracted, and expression of interleukin 1ß (IL-1ß), IL-6, and osteoprotegerin (OPG) was measured by RT-PCR. Results IL-1ß gene expression was significantly reduced by the T1 serum, and the same decrease was elicited by the T2 serum. IL-6 downregulation was evident with the T2 serum. OPG was unaffected. Conclusion The finding of downregulation of inflammatory cytokines was interesting, particularly IL-6, which plays a crucial role in arthritis-related bone loss due to its involvement in osteoclast recruitment and activation. These results may represent a biological explanation and a link for the clinical observation of the beneficial effects of anti-TNF-α agents on the progression of rheumatic diseases at the bone level. ER -