Cyclic mechanical stretching enhances secretion of Interleukin 6 in human tendon fibroblasts

Abstract

Accelerated rehabilitation after tendon and ligament injuries is widely accepted to avoid adverse effects of immobilization. However, progressive rehabilitation may also lead to an excessive inflammatory soft tissue response. To investigate the amount of loading necessary to accelerate the healing process without causing damage to the healing tissue, we experimentally stretched human tendon fibroblasts of healthy tendons 15 and 60 min with 1 Hz and an elongation of 5% and measured the secretion of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta1 (TGF-beta1), platelet-derived growth factor (PDGF), and fibroblast growth factor basic (bFGF). Secretion of IL-6 was significantly induced by 15 min of cyclic biaxial mechanical stretching after 4 and 8 h observation time and by 60 min stretching and 2 h observation time. The growth factors TGF-beta1, bFGF, and PDGF were secreted by human tendon fibroblasts both in stretched cells and controls; however, no increases were related to mechanical stretching. There was no measurable secretion of TNF-alpha in human tendon fibroblasts. These findings suggest that the inflammatory reaction often seen during physiotherapy after tendon and ligament injuries is caused in part by secretion of IL-6 from the stretched human tendon fibroblasts. IL-6 may cause exaggerated proliferation of fibroblasts and synovial cells as seen in rheumatoid arthritis and arthrofibrosis. However, physiological proliferative reactions leading to repair of injured tissue are also possible. IL-6 measured in the synovial fluid may be an important predictor for monitoring and improving therapeutic strategies in terms of tendon/ligament healing.