Show simple item record Allen, KD Adams, SB Mata, BA Shamji, MF Gouze, E Jing, L Nettles, DL Latt, LD Setton, LA
dc.coverage.spatial United States 2011-01-20T20:57:40Z 2011-05
dc.identifier.citation J Orthop Res, 2011, 29 (5), pp. 694 - 703
dc.description.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.
dc.description.sponsorship National Institutes of Health - R01EB002263, R21AR052745, P01AR050245, K99AR057426, F32AR056190. The North Carolina Biotechnology Center - CFG-8013. An OREF/DePuy Orthopaedic Resident Educational Grant. en_US
dc.format.extent 694 - 703
dc.language eng
dc.language.iso en_US en_US
dc.relation.ispartof J Orthop Res
dc.relation.isversionof 10.1002/jor.21309
dc.subject Animals
dc.subject Arthritis
dc.subject Behavior, Animal
dc.subject Disease Models, Animal
dc.subject Gait
dc.subject Hindlimb
dc.subject Humans
dc.subject Injections, Intra-Articular
dc.subject Interleukin 1 Receptor Antagonist Protein
dc.subject Interleukin-1beta
dc.subject Joints
dc.subject Pain
dc.subject Rats
dc.subject Rats, Wistar
dc.title Gait and behavior in an IL1β-mediated model of rat knee arthritis and effects of an IL1 antagonist.
dc.type Journal Article
pubs.issue 5
pubs.organisational-group /Duke
pubs.organisational-group /Duke/Institutes and Provost's Academic Units
pubs.organisational-group /Duke/Institutes and Provost's Academic Units/University Institutes and Centers
pubs.organisational-group /Duke/Institutes and Provost's Academic Units/University Institutes and Centers/Duke Institute for Brain Sciences
pubs.organisational-group /Duke/Pratt School of Engineering
pubs.organisational-group /Duke/Pratt School of Engineering/Biomedical Engineering
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Orthopaedics
pubs.publication-status Published
pubs.volume 29
dc.identifier.eissn 1554-527X

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