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

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

United States

2011-01-20T20:57:40Z

2011-05

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.

National Institutes of Health - R01EB002263, R21AR052745, P01AR050245, K99AR057426, F32AR056190. The North Carolina Biotechnology Center - CFG-8013. An OREF/DePuy Orthopaedic Resident Educational Grant.

http://www.ncbi.nlm.nih.gov/pubmed/21437948

1554-527X

https://hdl.handle.net/10161/3170

eng

en_US

Wiley

J Orthop Res

10.1002/jor.21309

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

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

Journal article

Adams, Samuel B|0000-0003-1020-1167

http://www.ncbi.nlm.nih.gov/pubmed/21437948

694

703

5

Biomedical Engineering

Clinical Science Departments

Duke

Duke Institute for Brain Sciences

Institutes and Provost's Academic Units

Orthopaedics

Pratt School of Engineering

School of Medicine

University Institutes and Centers

Published

29