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Gait and behavior in an IL1β-mediated model of rat knee arthritis and effects of an IL1 antagonist.

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Date
2011-05
Authors
Allen, Kyle D
Adams, Samuel B
Mata, Brian A
Shamji, Mohammed F
Gouze, Elvire
Jing, Liufang
Nettles, Dana L
Latt, L Daniel
Setton, Lori A
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Abstract
Interleukin-1 beta (IL1β) is a proinflammatory cytokine that mediates arthritic pathologies. Our objectives were to evaluate pain and limb dysfunction resulting from IL1β over-expression in the rat knee and to investigate the ability of local IL1 receptor antagonist (IL1Ra) delivery to reverse-associated pathology. IL1β over-expression was induced in the right knees of 30 Wistar rats via intra-articular injection of rat fibroblasts retrovirally infected with human IL1β cDNA. A subset of animals received a 30 µl intra-articular injection of saline or human IL1Ra on day 1 after cell delivery (0.65 µg/µl hIL1Ra, n = 7 per group). Joint swelling, gait, and sensitivity were investigated over 1 week. On day 8, animals were sacrificed and joints were collected for histological evaluation. Joint inflammation and elevated levels of endogenous IL1β were observed in knees receiving IL1β-infected fibroblasts. Asymmetric gaits favoring the affected limb and heightened mechanical sensitivity (allodynia) reflected a unilateral pathology. Histopathology revealed cartilage loss on the femoral groove and condyle of affected joints. Intra-articular IL1Ra injection failed to restore gait and sensitivity to preoperative levels and did not reduce cartilage degeneration observed in histopathology. Joint swelling and degeneration subsequent to IL1β over-expression is associated limb hypersensitivity and gait compensation. Intra-articular IL1Ra delivery did not result in marked improvement for this model; this may be driven by rapid clearance of administered IL1Ra from the joint space. These results motivate work to further investigate the behavioral consequences of monoarticular arthritis and sustained release drug delivery strategies for the joint space.
Type
Journal article
Subject
Animals
Arthritis
Behavior, Animal
Disease Models, Animal
Gait
Hindlimb
Humans
Injections, Intra-Articular
Interleukin 1 Receptor Antagonist Protein
Interleukin-1beta
Joints
Pain
Rats
Rats, Wistar
Permalink
https://hdl.handle.net/10161/3170
Published Version (Please cite this version)
10.1002/jor.21309
Publication Info
Allen, Kyle D; Adams, Samuel B; Mata, Brian A; Shamji, Mohammed F; Gouze, Elvire; Jing, Liufang; ... Setton, Lori A (2011). Gait and behavior in an IL1β-mediated model of rat knee arthritis and effects of an IL1 antagonist. J Orthop Res, 29(5). pp. 694-703. 10.1002/jor.21309. Retrieved from https://hdl.handle.net/10161/3170.
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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Scholars@Duke

Adams

Samuel Bruce Adams Jr.

Associate Professor of Orthopaedic Surgery

Lori A. Setton

Adjunct Professor of Biomedical Engineering
Research in Setton's laboratory is focused on the role of mechanical factors in the degeneration and repair of soft tissues of the musculoskeletal system, including the intervertebral disc, articular cartilage and meniscus. Work in the Laboratory is focused on engineering and evaluating materials for tissue regeneration and drug delivery. Studies combining engineering and biology are also used to determine the role of mechanical factors to promote and control healing of cartilaginous tissues. Re
Alphabetical list of authors with Scholars@Duke profiles.
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