title: A potential mode of action for Anakinra in patients with arthrofibrosis following total knee arthroplasty.
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.
authors.affiliation: Fibrosis Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: David
authors.initials: D
authors.lastname: Dixon
authors.affiliation: Fibrosis Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Jonathon
authors.initials: J
authors.lastname: Coates
authors.affiliation: Fibrosis Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Alicia
authors.initials: A
authors.lastname: del Carpio Pons
authors.affiliation: Fibrosis Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Horabin
authors.affiliation: Fibrosis Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Walker
authors.affiliation: Fibrosis Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.|Musculoskeletal Unit, Freeman Hospital, Newcastle Hospitals, NHS Trust, High Heaton, Newcastle upon Tyne NE7 7DN, UK.
authors.forename: Nicole
authors.initials: N
authors.lastname: Abdul
authors.affiliation: Fibrosis Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.|Musculoskeletal Unit, Freeman Hospital, Newcastle Hospitals, NHS Trust, High Heaton, Newcastle upon Tyne NE7 7DN, UK.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Kalson
authors.affiliation: Musculoskeletal Unit, Freeman Hospital, Newcastle Hospitals, NHS Trust, High Heaton, Newcastle upon Tyne NE7 7DN, UK.
authors.forename: Nigel T
authors.initials: NT
authors.lastname: Brewster
authors.affiliation: Musculoskeletal Unit, Freeman Hospital, Newcastle Hospitals, NHS Trust, High Heaton, Newcastle upon Tyne NE7 7DN, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Weir
authors.affiliation: Fibrosis Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.|Musculoskeletal Unit, Freeman Hospital, Newcastle Hospitals, NHS Trust, High Heaton, Newcastle upon Tyne NE7 7DN, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Deehan
authors.affiliation: Fibrosis Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Derek A
authors.initials: DA
authors.lastname: Mann
authors.affiliation: Fibrosis Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Lee A
authors.initials: LA
authors.lastname: Borthwick
mesh_terms: D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects; D015415:Biomarkers; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005355:Fibrosis; D015870:Gene Expression; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics / Q000378:metabolism*; D007592:Joint Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D007719:Knee Joint / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D008297:Male; D010641:Phenotype; D011184:Postoperative Period; D013583:Synovial Membrane / Q000166:cytology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein; D053773:Transforming Growth Factor beta1