Elevated proinflammatory cytokines in response to mechanical stimulus are associated with reduced knee loading 2 years after anterior cruciate ligament reconstruction

Abstract

Background

The aim of this study was to test the hypothesis that proinflammatory cytokines correlate with knee loading mechanics during gait following a mechanical walking stimulus in subjects 2 years after anterior cruciate ligament reconstruction. Elevated systemic levels of proinflammatory cytokines can be sustained for years after injury. Considering roughly 50% of these patients progress to Osteoarthritis 10–15 years after injury, a better understanding of the role of proinflammatory cytokines such as tumor necrosis factor-α and Interleukin-1β on Osteoarthritis risk is needed.

Methods

Serum proinflammatory cytokines concentrations were measured in 21 subjects 2 years after unilateral ACLR from blood drawn at rest and 3.5 h after 30 min of walking. An optoelectronic system and a force plate measured subjects' knee kinetics. Correlations were tested between inflammatory marker response and knee extension and knee adduction moments.

Findings

Changes in proinflammatory cytokines due to mechanical stimulus were correlated (R = 0.86) and showed substantial variation between subjects in both cytokines at 3.5 h post-walk. Knee loading correlated with 3.5-h changes in tumor necrosis factor-α concentration (Knee extension moment: R = -0.5, Knee adduction moment: R = -0.5) and Interleukin-1β concentration (Knee extension moment: R = -0.44). However, no significant changes in concentrations were observed in tumor necrosis factor-α and Interleukin-1β when comparing baseline and post walking stimulus conditions.

Interpretation

The significant associations between changes in serum proinflammatory markers following a mechanical stimulus and gait metrics in subjects at risk for developing Osteoarthritis underscore the importance of investigating the interaction between biomarkers and biomechanical factors in Osteoarthritis development.