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Cytokine production by infrapatellar fat pad can be stimulated by interleukin 1β and inhibited by peroxisome proliferator activated receptor α agonist
  1. Stefan Clockaerts1,2,
  2. Yvonne M Bastiaansen-Jenniskens2,
  3. Carola Feijt2,
  4. Luc De Clerck3,
  5. J A N Verhaar2,
  6. Anne-Marie Zuurmond4,
  7. Vedrana Stojanovic-Susulic5,
  8. Johan Somville1,
  9. Margreet Kloppenburg6,
  10. Gerjo J V M van Osch7
  1. 1Department of Orthopaedic Surgery and Traumatology, University of Antwerp, Antwerp, Belgium
  2. 2Department of Orthopaedics, Erasmus MC, Rotterdam, Netherlands
  3. 3Department of Rheumatology, University of Antwerp, Antwerp, Belgium
  4. 4TNO, Leiden, Netherlands
  5. 5Centocor Research & Development, A division of Johnson & Johnson Pharmaceutical Research & Development, L L C, Malvern, Pennsylvania, USA
  6. 6Leiden University Medical Center, Department of Rheumatology, Leiden, Netherlands
  7. 7Orthopaedics and Otorhinolaryngology, Erasmus MC, Rotterdam, Netherlands
  1. Correspondence to Stefan Clockaerts, University of Antwerp, Orthopaedic Surgery and Traumatology, Antwerp, Belgium; s.clockaerts{at}erasmusmc.nl

Abstract

Background Infrapatellar fat pad (IPFP) might be involved in osteoarthritis (OA) by production of cytokines. It was hypothesised that production of cytokines is sensitive to environmental conditions.

Objectives To evaluate cytokine production by IPFP in response to interleukin (IL)1β and investigate the ability to modulate this response with an agonist for peroxisome proliferator activated receptor α (PPARα), which is also activated by lipid-lowering drugs such as fibrates.

Methods Cytokine secretion of IPFP was analysed in the medium of explant cultures of 29 osteoarthritic patients. IPFP (five donors) and synovium (six donors) were cultured with IL-1β and PPARα agonist Wy14643. Gene expression of IL-1β, monocyte chemoattractant protein (MCP1), (IL-6, tumour necrosis factor (TNF)α, leptin, vascular endothelial growth factor (VEGF), IL-10, prostaglandin-endoperoxide synthase (PTGS)2 and release of TNFα, MCP1 and prostaglandin E2 were compared with unstimulated IPFP and synovium explants.

Results IPFP released large amounts of inflammatory cytokines, adipokines and growth factors. IL-1β increased gene expression of PTGS2, TNFα, IL-1β, IL-6 and VEGF and increased TNFα release in IPFP. MCP1, leptin, IL-10 gene expression and MCP1, leptin and PGE2 release did not increase significantly. Synovium responded to IL-1β similarly to IPFP, except for VEGF gene expression. Wy14643 decreased gene expression of PTGS2, IL-1β, TNFα, MCP1, VEGF and leptin in IPFP explants and IL-1β, TNFα, IL-6, IL-10 and VEGF in synovium that responded to IL-1β.

Conclusion IPFP is an active tissue within the joint. IPFP cytokine production is increased by IL-1β and decreased by a PPARα agonist. The effects were similar to effects seen in synovium. Fibrates may represent a potential disease-modifying drug for OA by modulating inflammatory properties of IPFP and synovium.

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Footnotes

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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