Restoring knee stability through reconstruction, while providing symptomatic relief, has not been shown to decrease the incidence of degenerative changes after
rupture of the anterior cruciate ligament. This suggests that posttraumatic
osteoarthritis may not be purely biomechanical in origin, but also biochemical. To test this, we measured the levels of seven
cytokine modulators of cartilage metabolism in knee joint synovial fluid after anterior cruciate ligament
rupture. We also measured
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 samples were analyzed by
enzyme-linked
immunosorbent assays. Normal synovial fluids contained high levels of the
interleukin-1 receptor antagonist but low concentrations of other
cytokines. Immediately after ligament
rupture there were large increases in
interleukins 6 and 8,
tumor necrosis factor alpha, and
keratan sulfate.
Interleukin-1 levels remained low throughout the course. As the injury became subacute and then chronic,
interleukin-6,
tumor necrosis factor-alpha, and
keratan sulfate levels fell but remained considerably elevated 3 months after injury. Concentrations of interleukin-1Ra fell dramatically.
Granulocyte-macrophage colony-stimulating factor concentrations were normal acutely and subacutely but by 3 months after injury were elevated 10-fold. Our data reveal a persistent and evolving disturbance in
cytokine and
keratan sulfate profiles within the anterior cruciate ligament-deficient knee, suggesting an important biochemical dimension to the development of
osteoarthritis there.