RT Journal Article
SR Electronic
T1 The Tumor Necrosis Factor-α-blocking Agent Infliximab Inhibits Interleukin 1ß (IL-1ß) and IL-6 Gene Expression in Human Osteoblastic Cells
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 1575
OP 1579
DO 10.3899/jrheum.081321
VO 36
IS 8
A1 ESTELLA MUSACCHIO
A1 CHIARA VALVASON
A1 CONSTANTIN BOTSIOS
A1 FRANCESCA OSTUNI
A1 ANTONIO FURLAN
A1 ROBERTA RAMONDA
A1 VALENTINA MODESTI
A1 LEONARDO SARTORI
A1 LEONARDO PUNZI
YR 2009
UL http://www.jrheum.org/content/36/8/1575.abstract
AB 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 RA also 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.