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


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.





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Publication Info

Furman, Bridgette D, Daniel S Mangiapani, Evan Zeitler, Karsyn N Bailey, Phillip H Horne, Janet L Huebner, Virginia B Kraus, Farshid Guilak, et al. (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). p. R134. 10.1186/ar4591 Retrieved from

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Virginia Byers Kraus

Mary Bernheim Distinguished Professor of Medicine

Virginia Byers Kraus, MD, PhD, is the Mary Bernheim Distinguished Professor of Medicine, Professor of Orthopaedic Surgery, Professor of Pathology and a faculty member of the Duke Molecular Physiology Institute in the Duke University School of Medicine. She is a practicing Rheumatologist with over 30 years’ experience in translational musculoskeletal research focusing on osteoarthritis, the most common of all arthritides. She trained at Brown University (ScB 1979), Duke University (MD 1982, PhD 1993) and the Duke University School of Medicine (Residency in Internal Medicine and Fellowship in Rheumatology). Her career has focused on elucidating osteoarthritis pathogenesis and translational research into the discovery and validation of biomarkers for early osteoarthritis detection, prediction of progression, monitoring of disease status, and facilitation of therapeutic developments. She is co-PI of the Foundation for NIH Biomarkers Consortium Osteoarthritis project. Trained as a molecular biologist and a Rheumatologist, she endeavors to study disease from bedside to bench.


Steven Arthur Olson

Goldner Jones Distinguished Professor of Orthopaedic Surgery

As an Orthopedic Surgeon my primary focus of research is joint preservation. My primary clinical interests are Orthopedic Trauma and Hip Reconstruction.

In Orthopedic 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 my areas of research are 1) Hip Arthroscopy and treatment of hip disorders, and treatment of labral tears in the treatment of hip pain. 2) Periacetabular osteotomy for the treatment of hip dysplasia.

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