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

Furman, Bridgette D

Mangiapani, Daniel S

Zeitler, Evan

Bailey, Karsyn N

Horne, Phillip H

Huebner, Janet L

Kraus, Virginia B

Guilak, Farshid

Olson, Steven A

England

2015-11-10T22:29:15Z

2014-06-25

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.

http://www.ncbi.nlm.nih.gov/pubmed/24964765

ar4591

1478-6362

https://hdl.handle.net/10161/10865

eng

Springer Science and Business Media LLC

Arthritis Res Ther

10.1186/ar4591

Animals

Antirheumatic Agents

Arthritis, Experimental

Etanercept

Fractures, Closed

Immunoglobulin G

Inflammation Mediators

Injections, Intra-Articular

Interleukin 1 Receptor Antagonist Protein

Interleukin-1

Intra-Articular Fractures

Knee Injuries

Knee Joint

Male

Mice, Inbred C57BL

Receptors, Tumor Necrosis Factor

Synovitis

Treatment Outcome

Tumor Necrosis Factor-alpha

X-Ray Microtomography

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

Journal article

Kraus, Virginia B|0000-0001-8173-8258

Olson, Steven A|0000-0003-2236-0667

http://www.ncbi.nlm.nih.gov/pubmed/24964765

R134

3

Biomedical Engineering

Clinical Science Departments

Duke

Duke Molecular Physiology Institute

Institutes and Centers

Medicine

Medicine, Rheumatology and Immunology

Orthopaedics

Pathology

Pratt School of Engineering

School of Medicine

Published online

16