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Long term NSAID treatment inhibits COX-2 synthesis in the knee synovial membrane of patients with osteoarthritis: differential proinflammatory cytokine profile between celecoxib and aceclofenac
  1. M A Álvarez-Soria1,*,
  2. R Largo1,*,
  3. J Santillana2,
  4. O Sánchez-Pernaute1,
  5. E Calvo1,
  6. M Hernández2,
  7. J Egido1,
  8. G Herrero-Beaumont1
  1. 1Joint and Bone Research Unit, Fundación Jiménez Díaz, Autonomous University, Madrid, Spain
  2. 2Orthopaedic Surgery Department, Hospital Virgen de la Cinta, Tortosa, Tarragona, Spain
  1. Correspondence to:
    Dr G Herrero-Beaumont
    Servicio de Reumatología, Fundación Jiménez Díaz Avenida Reyes Católicos 2, 28040 Madrid, Spain; gherrero{at}fjd.es

Abstract

Objective: To compare the effect of celecoxib with that of a classic non-steroidal anti-inflammatory drug (NSAID) on synovial inflammation and on the synovial expression of proinflammatory genes in patients with knee osteoarthritis (OA).

Methods: 30 patients with severe knee OA scheduled for total knee replacement surgery were included in a 3 month clinical trial. They were randomised to two groups: patients treated with celecoxib (CBX) (200 mg/24 h) and patients treated with aceclofenac (ACF) (100 mg/12 h). Those patients with OA who did not want to be treated with NSAIDs served as a control group. During knee surgery, synovial fluid (SF) and synovial membrane (SM) were collected. A SM specimen was fixed and embedded in paraffin and another part was frozen for molecular biology studies.

Results: At the end of study both CBX and ACF treated patients showed a significant improvement in pain and knee function compared with controls. Both drugs significantly reduced prostaglandin E2 (PGE2) SF concentration and down regulated COX-2 mRNA and protein expression at the SM. However, synovial macrophage infiltration (CD68 antigen staining) and expression of proinflammatory mediators, such as interleukin 1β and tumour necrosis factor α, were decreased only by CBX treatment.

Conclusion: Both drugs improved joint pain and function, inhibited SF PGE2 concentration, and induced a decrease in synovial COX-2 expression and synthesis not related to the tissue inflammatory status. These data suggest that PGE2 blocking agents may decrease PGE2 production not only by direct COX-2 inhibition but also by down regulating COX-2 expression and synthesis. However, CBX and ACF appear to have different anti-inflammatory profiles in controlling OA synovial macrophage infiltration and proinflammatory expression.

  • ACF, aceclofenac
  • CBX, celecoxib
  • COX, cyclo-oxygenase
  • IL, interleukin
  • NSAIDs, non-steroidal anti-inflammatory drugs
  • OA, osteoarthritis
  • PCR, polymerase chain reaction
  • PG, prostaglandin
  • SF, synovial fluid
  • SM, synovial membrane
  • TNF, tumour necrosis factor
  • WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index
  • osteoarthritis
  • COX-2
  • synovial membrane
  • non-steroidal anti-inflammatory drugs
  • celecoxib

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Footnotes

  • * Both authors contributed equally to this work

  • Published Online First 13 February 2006

  • Ethics approval: the local ethics committee approved the study, and informed consent was obtained from all patients.

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