Gait and behavior in an IL1β-mediated model of rat knee arthritis and effects of an IL1 antagonist.
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 articleSubject
AnimalsArthritis
Behavior, Animal
Disease Models, Animal
Gait
Hindlimb
Humans
Injections, Intra-Articular
Interleukin 1 Receptor Antagonist Protein
Interleukin-1beta
Joints
Pain
Rats
Rats, Wistar
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https://hdl.handle.net/10161/3170Published Version (Please cite this version)
10.1002/jor.21309Publication 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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Show full item recordScholars@Duke
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
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