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A potential mode of action for Anakinra in patients with arthrofibrosis following total knee arthroplasty

Lookup NU author(s): David Dixon, Jonathon Coates, Joanna Horabin, Andrew Walker, Dr Nicole Abdul, Dr Nicholas Kalson, Professor David Deehan, Professor Derek Mann, Dr Lee Borthwick

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Abstract

Arthrofibrosis is a fibroproliferative disease characterised by excessive deposition of extracellular matrix components intra-articularly leading to pain and restricted range of movement. Although frequently observed following total knee arthroplasty (TKA) no therapeutic options exist. A pilot study demonstrated that intra-articular injection of Anakinra, an IL-1R antagonist, improved range of movement and pain in patients with arthrofibrosis however the mechanism of action is unknown. We hypothesise that IL-1 alpha/beta will drive an inflammatory phenotype in fibroblasts isolated from the knee, therefore identifying a potential mechanism of action for Anakinra in arthrofibrosis following TKA. Fibroblasts isolated from synovial membranes and infra-patellar fat pad of patients undergoing TKA express high levels of IL-1R1. Stimulation with IL-1 alpha/beta induced a pro-inflammatory phenotype characterised by increased secretion of GMCSF, IL-6 and IL-8. No significant difference in the inflammatory response was observed between fibroblasts isolated from synovial membrane or infrapatellar fat pad. IL-1 alpha/beta treatments induced a pro-inflammatory phenotype in fibroblasts from both synovial membrane and infra-patellar fat pad and therefore Anakinra can likely have an inhibitory effect on fibroblasts present in both tissues in vivo. It is also likely that fibroblast responses in the tissues are controlled by IL-1 alpha/beta availability and not their ability to respond to it.

Publication metadata

Author(s): Dixon D, Coates J, Pons AD, Horabin J, Walker A, Abdul N, Kalson NS, Brewster NT, Weir DJ, Deehan DJ, Mann DA, Borthwick LA

Publication type: Article

Publication status: Published

Journal: Scientific Reports

Year: 2015

Volume: 5

Online publication date: 10/11/2015

Acceptance date: 05/10/2015

Date deposited: 01/03/2016

ISSN (electronic): 2045-2322

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/srep16466

DOI: 10.1038/srep16466

PubMed id: 26553966

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