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

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/ß 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/ß 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/ß 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/ß availability and not their ability to respond to it.

Fibrosis is a common outcome following total knee arthroplasty.

Total knee arthroplasty (TKA) is one of the most successful orthopaedic procedures that alleviates pain and restores function in patients with degenerative knee joint diseases. Arthrofibrosis, abnormal scarring in which dense fibrous tissue prevents normal range of motion, develops in ~3-10% of TKA patients. No prophylactic intervention is available and treatment is restricted to aggressive physiotherapy or revision surgery. Tissue was collected from patients undergoing primary (n = 30) or revision (n = 27) TKA. Revision patients were stratified as non-arthrofibrotic and arthrofibrotic. Tissue was macroscopically and histologically compared to improve our understanding of the pathophysiology of arthrofibrosis. Macroscopically, tissue from primary TKA presents as homogenous, fatty tissue whereas tissue from revision TKA presents as dense, pigmented tissue. Histologically, there was dramatic tissue remodelling, increased collagen deposition and increased (myo)fibroblast staining in tissue from revision TKA. Significantly, tissue architecture was similar between revision patients regardless of clinically diagnosis. There are significant differences in architecture and composition of tissue from revision TKA over primary TKA. Surprisingly, whether revision TKA were clinically diagnosed as arthrofibrotic or non-arthrofibrotic there were still significant differences in fibrotic markers compared to primary TKA suggesting an ongoing fibrotic process in all revision knees.