IntroductionPost-traumatic arthritis (PTA) is a progressive, degenerative response to joint injury, such as articular fracture. The pro-inflammatory cytokines, interleukin 1(IL-1) and tumor necrosis factor alpha (TNF-α), are acutely elevated following joint injury and remain elevated for prolonged periods post-injury. To investigate the role of local and systemic inflammation in the development of post-traumatic arthritis, we targeted both the initial acute local inflammatory response and a prolonged 4 week systemic inflammatory response by inhibiting IL-1 or TNF-α following articular fracture in the mouse knee.MethodsAnti-cytokine agents, IL-1 receptor antagonist (IL-1Ra) or soluble TNF receptor II (sTNFRII), were administered either locally via an acute intra-articular injection or systemically for a prolonged 4 week period following articular fracture of the knee in C57BL/6 mice. The severity of arthritis was then assessed at 8 weeks post-injury in joint tissues via histology and micro computed tomography, and systemic and local biomarkers were assessed in serum and synovial fluid.ResultsIntra-articular inhibition of IL-1 significantly reduced cartilage degeneration, synovial inflammation, and did not alter bone morphology following articular fracture. However, systemic inhibition of IL-1, and local or systemic inhibition of TNF provided no benefit or conversely led to increased arthritic changes in the joint tissues.ConclusionThese results show that intra-articular IL-1, rather than TNF-α, plays a critical role in the acute inflammatory phase of joint injury and can be inhibited locally to reduce post-traumatic arthritis following a closed articular fracture. Targeted local inhibition of IL-1 following joint injury may represent a novel treatment option for PTA.

The development of arthritis after joint injury is commonly known as posttraumatic arthritis (PTA). The inciting traumatic event may range from cartilage contusion and bone bruise combined with meniscus or ligament tear, to intra-articular fracture. End-stage PTA is often indistinguishable from primary osteoarthritis. However, knowing the time of the inciting traumatic event in a patient with PTA provides an opportunity to understand the events following joint injury that lead to the progression of arthritis. Joint injury often leads to mechanical alterations in loading of the injured joint, and restoration of joint mechanics through surgical repair remains an important aspect of treatment. However, the accuracy of joint reduction by itself does not account for the variability in outcome following joint injury, as evidenced by the fact that PTA remains a significant clinical problem. Emerging research in animal models and human subjects indicates that several inflammatory cytokines and related inflammatory mediators are elevated following joint injury. Data from animal studies and early clinical trials suggest that early inhibition of the intra-articular inflammatory response may improve clinical outcomes.