The tumor necrosis factor-{alpha}-blocking agent infliximab inhibits interleukin 1beta (IL-1beta) and IL-6 gene expression in human osteoblastic cells.
OBJECTIVE
Tumor necrosis factor-alpha (TNF-alpha) 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-alpha-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 1beta (IL-1beta), IL-6, and osteoprotegerin (OPG) was measured by RT-PCR.


RESULTS
IL-1beta 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.


CONCLUSIONS
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-alpha agents on the progression of rheumatic diseases at the bone level.
Musacchio
Estella
E
Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy.
Valvason
Chiara
C
Botsios
Constantin
C
Ostuni
Francesca
F
Furlan
Antonio
A
Ramonda
Roberta
R
Modesti
Valentina
V
Sartori
Leonardo
L
Punzi
Leonardo
L
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001798:Blood Proteins / Q000494:pharmacology; D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D000069285:Infliximab; D020382:Interleukin-18 / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D053244:Osteoprotegerin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044967:Serum; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects*
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D001798:Blood Proteins; C508600:IL6 protein, human; D020382:Interleukin-18; D053583:Interleukin-1beta; D015850:Interleukin-6; D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab