THE NATURAL-HISTORY OF THE ANTERIOR CRUCIATE LIGAMENT-DEFICIENT KNEE - CHANGES IN SYNOVIAL-FLUID CYTOKINE AND KERATAN SULFATE CONCENTRATIONS

Restoring knee stability through reconstruction, while providing sympt omatic relief, has not been shown to decrease the incidence of degener ative changes after rupture of the anterior cruciate ligament. This su ggests that posttraumatic osteoarthritis may not be purely biomechanic al in origin, but also biochemical. To test this, we measured the leve ls of seven cytokine modulators of cartilage metabolism in knee joint synovial fluid after anterior cruciate ligament rupture. We also measu red keratan sulfate, a product of articular cartilage catabolism, The sample population consisted of patients with uninjured knee joints (N 10), and patients with acute (N = 60), subacute (N = 18), and chronic (N = 8) anterior cruciate ligament-deficient knees, Synovial fluid sam ples were analyzed by enzyme-linked immunosorbent assays. Normal synov ial fluids contained high levels of the interleukin-l receptor antagon ist but low concentrations of other cytokines. Immediately after ligam ent rupture there were large increases in interleukins 6 and 8, tumor necrosis factor alpha, and keratan sulfate, Interleukin-l levels remai ned low throughout the course. As the injury became subacute and then chronic, interleukin-6, tumor necrosis factor-alpha, and keratan sulfa te levels fell but remained considerably elevated 3 months after injur y, Concentrations of interleukin-1Ra fell dramatically. Granulocyte-ma crophage colony-stimulating factor concentrations were normal acutely and subacutely but by 3 months after injury were elevated IO-fold, Our data reveal a persistent and evolving disturbance in cytokine and ker atan sulfate profiles within the anterior cruciate ligament-deficient knee, suggesting an important biochemical dimension to the development of osteoarthritis there.