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Targeting pro-inflammatory cytokines following joint injury: acute intra-articular inhibition of interleukin-1 following knee injury prevents post-traumatic arthritis.

dc.contributor.author Bailey, KN
dc.contributor.author Furman, BD
dc.contributor.author Guilak, Farshid
dc.contributor.author Horne, PH
dc.contributor.author Huebner, JL
dc.contributor.author Kraus, Virginia Byers
dc.contributor.author Mangiapani, DS
dc.contributor.author Olson, Steven Arthur
dc.contributor.author Zeitler, E
dc.coverage.spatial England
dc.date.accessioned 2015-11-10T22:29:15Z
dc.date.issued 2014-06-25
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/24964765
dc.identifier ar4591
dc.identifier.uri https://hdl.handle.net/10161/10865
dc.description.abstract 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.
dc.language eng
dc.relation.ispartof Arthritis Res Ther
dc.relation.isversionof 10.1186/ar4591
dc.subject Animals
dc.subject Antirheumatic Agents
dc.subject Arthritis, Experimental
dc.subject Etanercept
dc.subject Fractures, Closed
dc.subject Immunoglobulin G
dc.subject Inflammation Mediators
dc.subject Injections, Intra-Articular
dc.subject Interleukin 1 Receptor Antagonist Protein
dc.subject Interleukin-1
dc.subject Intra-Articular Fractures
dc.subject Knee Injuries
dc.subject Knee Joint
dc.subject Male
dc.subject Mice, Inbred C57BL
dc.subject Receptors, Tumor Necrosis Factor
dc.subject Synovitis
dc.subject Treatment Outcome
dc.subject Tumor Necrosis Factor-alpha
dc.subject X-Ray Microtomography
dc.title Targeting pro-inflammatory cytokines following joint injury: acute intra-articular inhibition of interleukin-1 following knee injury prevents post-traumatic arthritis.
dc.type Journal article
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/24964765
pubs.begin-page R134
pubs.issue 3
pubs.organisational-group Biomedical Engineering
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Molecular Physiology Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Rheumatology and Immunology
pubs.organisational-group Orthopaedics
pubs.organisational-group Pathology
pubs.organisational-group Pratt School of Engineering
pubs.organisational-group School of Medicine
pubs.publication-status Published online
pubs.volume 16
dc.identifier.eissn 1478-6362


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