Targeting pro-inflammatory cytokines following joint injury: acute intra-articular inhibition of interleukin-1 following knee injury prevents post-traumatic arthritis.
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.
Type
Journal articleSubject
AnimalsAntirheumatic 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
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https://hdl.handle.net/10161/10865Published Version (Please cite this version)
10.1186/ar4591Publication Info
Furman, Bridgette D; Mangiapani, Daniel S; Zeitler, Evan; Bailey, Karsyn N; Horne,
Phillip H; Huebner, Janet L; ... Olson, Steven A (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.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Farshid Guilak
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.
Virginia Byers Kraus
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
Steven Arthur Olson
Goldner Jones Distinguished 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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