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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-1?/? 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?/? 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-1?/? 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?/? availability and not their ability to respond to it.

SUBMITTER: Dixon D

PROVIDER: S-EPMC4639732 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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

Dixon David D Coates Jonathon J del Carpio Pons Alicia A Horabin Joanna J Walker Andrew A Abdul Nicole N Kalson Nicholas S NS Brewster Nigel T NT Weir David J DJ Deehan David J DJ Mann Derek A DA Borthwick Lee A LA

Scientific reports 20151110

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 hypoth ...[more]

PMID: 26553966

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Project description:IntroductionThe objective of this study was to assess the number and magnitude of preoperative expectations and to correlate them with the degree of satisfaction expressed one year after Total Hip Arthroplasty (THA) or Total Knee Arthroplasty (TKA), in patients with severe and painful osteoarthritis (OA).Materials and methodsPreoperative expectations (within 20 days prior to surgery) and postoperative satisfaction (one year after the intervention) were measured using the previously validated French version of the Hospital for Special Surgery Hip or Knee Replacement Expectations Survey. Postoperative satisfaction was measured using a specific scale, following the same methodology as that used for the assessment of expectations. Prediction of the satisfaction of the patients was performed using multivariate linear regression modelling.ResultsA total of 138 patients (80 THA and 58 TKA) completed the two parts of the study. The expectations score (mean ± SD) (range 0-100) was 72.58 ± 12.63 before THA and 69.10 ± 13.72 before TKA (p = 0.13). The number of expectations expressed was 14.34 ± 1.32 (out of a potential maximum of 18) before THA and 14.70 ± 2.29 (out of a potential maximum of 19) before TKA. After 1 year, THA generated a significantly higher degree of satisfaction compared to TKA (69.70 ± 14.46 v 60.44 ± 17.54, p<0.001) (range 0-100). The pre-operative expectations score was the single best positive predictor of the post-surgery satisfaction assessment both for TKA and THA.ConclusionPatients undergoing total joint arthroplasty for end-stage OA have a high level of expectations, before both THA and TKA. While both types of interventions significantly improve essential and non-essential activities, the rate of satisfaction is significantly greater post THA. Preoperative expectations are a major contributor to the final degree of satisfaction, one year after surgery. These results re-emphasize the need for an optimal preoperative interaction between health care providers and patients, to allow patients a chance to foresee a reasonable outcome after TJA.

Dataset Information

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

Publications

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

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