Targeting pro-inflammatory cytokines following joint injury: acute intra-articular inhibition of interleukin-1 following knee injury prevents post-traumatic arthritis.
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INTRODUCTION: Post-traumatic arthritis (PTA) is a progressive, degenerative response to joint injury, such as articular fracture. The pro-inflammatory cytokines, interleukin 1(IL-1) and tumor necrosis factor alpha (TNF-α), are acutely elevated following joint injury and remain elevated for prolonged periods post-injury. To investigate the role of local and systemic inflammation in the development of post-traumatic arthritis, we targeted both the initial acute local inflammatory response and a prolonged 4 week systemic inflammatory response by inhibiting IL-1 or TNF-α following articular fracture in the mouse knee. METHODS: Anti-cytokine agents, IL-1 receptor antagonist (IL-1Ra) or soluble TNF receptor II (sTNFRII), were administered either locally via an acute intra-articular injection or systemically for a prolonged 4 week period following articular fracture of the knee in C57BL/6 mice. The severity of arthritis was then assessed at 8 weeks post-injury in joint tissues via histology and micro computed tomography, and systemic and local biomarkers were assessed in serum and synovial fluid. RESULTS: Intra-articular inhibition of IL-1 significantly reduced cartilage degeneration, synovial inflammation, and did not alter bone morphology following articular fracture. However, systemic inhibition of IL-1, and local or systemic inhibition of TNF provided no benefit or conversely led to increased arthritic changes in the joint tissues. CONCLUSION: These results show that intra-articular IL-1, rather than TNF-α, plays a critical role in the acute inflammatory phase of joint injury and can be inhibited locally to reduce post-traumatic arthritis following a closed articular fracture. Targeted local inhibition of IL-1 following joint injury may represent a novel treatment option for PTA.
Interleukin 1 Receptor Antagonist Protein
Mice, Inbred C57BL
Receptors, Tumor Necrosis Factor
Tumor Necrosis Factor-alpha
Published Version (Please cite this version)10.1186/ar4591
Publication InfoBailey, KN; Furman, BD; Guilak, Farshid; Horne, PH; Huebner, JL; Kraus, Virginia Byers; ... Zeitler, E (2014). Targeting pro-inflammatory cytokines following joint injury: acute intra-articular inhibition of interleukin-1 following knee injury prevents post-traumatic arthritis. Arthritis Res Ther, 16(3). pp. R134. 10.1186/ar4591. Retrieved from https://hdl.handle.net/10161/10865.
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Lazlo Ormandy Professor of Orthopaedic Surgery
This author no longer has a Scholars@Duke profile, so the information shown here reflects their Duke status at the time this item was deposited.
Clinical Associate in the Department of Orthopaedic Surgery
Professor of Medicine
My special area of expertise is as a clinician scientist investigating osteoarthritis. Osteoarthritis is the most common form of joint disease in man and its incidence increases with age. It is a problem of increasing concern to the medical community due to the increasing longevity of the population. Trained as a molecular biologist and a Rheumatologist, I endeavor to study this disease from bedside to bench. The work in this laboratory focuses on osteoarthritis and deals w
Professor of Orthopaedic Surgery
As an Orthopaedic Surgeon my primary focus of research is joint preservation. My primary clinical interests are Orthopaedic Trauma and Hip Reconstruction. In Orthopaedic Trauma my research interests are 1) Basic science investigations of articular fractures with two current animal models in use. 2) Clinical research includes evaluation of techniques to reduce and stabilize articular fractures, as well as management of open fractures. In the area of Hip Reconstruction
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