title: The tumor necrosis factor-{alpha}-blocking agent infliximab inhibits interleukin 1beta (IL-1beta) and IL-6 gene expression in human osteoblastic cells.
abstract: 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.
authors: Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy.
authors: Estella
authors: E
authors: Musacchio
authors: Chiara
authors: C
authors: Valvason
authors: Constantin
authors: C
authors: Botsios
authors: Francesca
authors: F
authors: Ostuni
authors: Antonio
authors: A
authors: Furlan
authors: Roberta
authors: R
authors: Ramonda
authors: Valentina
authors: V
authors: Modesti
authors: Leonardo
authors: L
authors: Sartori
authors: Leonardo
authors: L
authors: Punzi
mesh_terms: 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*
chemical_list: 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