Title |
A potential mode of action for Anakinra in patients with arthrofibrosis following total knee arthroplasty
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Published in |
Scientific Reports, November 2015
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DOI | 10.1038/srep16466 |
Pubmed ID | |
Authors |
David Dixon, Jonathon Coates, Alicia del Carpio Pons, Joanna Horabin, Andrew Walker, Nicole Abdul, Nicholas S. Kalson, Nigel T. Brewster, David J. Weir, David J. Deehan, Derek A. Mann, Lee A. Borthwick |
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-1α/β 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-1α/β 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 infra-patellar fat pad. IL-1α/β 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-1α/β availability and not their ability to respond to it. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United Kingdom | 2 | 50% |
Unknown | 2 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 4 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 47 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Postgraduate | 6 | 13% |
Student > Ph. D. Student | 5 | 11% |
Student > Doctoral Student | 5 | 11% |
Student > Bachelor | 4 | 9% |
Researcher | 4 | 9% |
Other | 13 | 28% |
Unknown | 10 | 21% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 19 | 40% |
Biochemistry, Genetics and Molecular Biology | 4 | 9% |
Agricultural and Biological Sciences | 2 | 4% |
Immunology and Microbiology | 2 | 4% |
Engineering | 2 | 4% |
Other | 5 | 11% |
Unknown | 13 | 28% |