Single Intra-Articular Anakinra (IL-1Ra) Versus Betamethasone in Rabbit Post-Traumatic Knee Osteoarthritis: IL-8...

Post-traumatic osteoarthritis (OA) is driven by a sustained inflammatory response and progressive osteochondral damage. We compared the effects of a single intra-articular injection of anakinra (Interleukin-1 receptor antagonist; IL-1Ra) with those of betamethasone on structural cartilage outcomes and Interleukin-8 (IL-8) immunopositivity in a rabbit model of post-traumatic knee OA, and assessed the cytotoxicity of anakinra in primary human OA chondrocytes. Fifteen male New Zealand White rabbits underwent bilateral anterior cruciate ligament transection and partial medial meniscectomy and were randomized to receive saline (OA, control), betamethasone (0.5 mg/kg), or anakinra (0.6 mg/kg) at 2 weeks post-surgery (n = 5 rabbits/group; 10 knees/group, clustered within rabbit). At 14 weeks, cartilage damage was graded using the Osteoarthritis Research Society International (OARSI) cartilage OA pathology assessment system, and IL-8 immunopositivity in cartilage was quantified by immunohistochemistry. In vitro, chondrocytes from seven donors (Passages 0-1) were treated with anakinra (1 µM to 1 mM) for 24 h, and cell viability was evaluated by MTT and neutral red uptake (NRU) assays. Both anakinra and betamethasone shifted the OARSI grade distribution toward lower grades compared with OA (p < 0.001), with no difference between the treatments (p = 0.639). IL-8 immunopositivity was lower with both treatments and was lowest in the anakinra group (OA: 93.09 ± 6.1%; betamethasone: 22.93 ± 3.4%; anakinra: 9.58 ± 3.9%) (p < 0.01 OA vs. betamethasone; p < 0.001 OA vs. anakinra). Anakinra did not reduce chondrocyte viability at concentrations up to 500 µM (p > 0.05), whereas 1 mM reduced viability by approximately 10% (p < 0.05). These findings suggest that a single-dose intra-articular anakinra injection modulates the histomorphological characteristics of damaged cartilage by preserving chondrocyte viability and inhibiting IL-8 expression in post-traumatic knee OA.