Improved Understanding of the Inflammatory Response in Synovial Fluid and Serum after Traumatic Knee Injury, Excluding Fractures of the Knee: A Systematic Review

Background Traumatic knee injury results in a 4- to 10-fold increased risk of post-traumatic osteoarthritis (PTOA). Currently, there are no successful interventions for preventing PTOA after knee injury. The aim of this study is to identify inflammatory proteins that are increased in serum and synovial fluid after acute knee injury, excluding intra-articular fractures. Methods A literature search was done according to the PRISMA guidelines. Articles reporting about inflammatory proteins after knee injury, except fractures, up to December 8, 2021 were collected. Inclusion criteria were as follows: patients younger than 45 years, no radiographic signs of knee osteoarthritis at baseline, and inflammatory protein measurement within 1 year after trauma. Risk of bias was assessed of the included studies. The level of evidence was determined by the Strength of Recommendation Taxonomy. Results Ten studies were included. All included studies used a healthy control group or the contralateral knee as healthy control. Strong evidence for interleukin 6 (IL-6) and limited evidence for CCL4 show elevated concentrations of these proteins in synovial fluid (SF) after acute knee injury; no upregulation in SF for IL-2, IL-10, CCL3, CCL5, CCL11, granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) was found. Limited evidence was found for no difference in serum concentration of IL-1β, IL-6, IL-10, CCL2, and tumor necrosis factor alpha (TNF-α) after knee injury. Conclusion Interleukin 6 and CCL4 are elevated in SF after acute knee injury. Included studies failed to demonstrate increased concentration of inflammatory proteins in SF samples taken 6 weeks after trauma. Future research should focus on SF inflammatory protein measurements taken less than 6 weeks after injury.