Local ice cryotherapy decreases synovial interleukin 6, interleukin 1β, vascular endothelial growth factor, prostaglandin-E2, and nuclear factor kappa B p65 in human knee arthritis: a controlled study

摘要

Background: The aim of this study was to assess the anti-inflammatory effects of local cryotherapy in human nonsepticknee arthritis.Methods: In the phase I of the study, patients were randomized to receive either ice (30 min; N = 16) or cold CO2(2 min; N = 16) applied twice during 1 day at an 8-h interval on the arthritic knee. In phase II, 16 other ice-treatedarthritic knees according to the same protocol were compared to the contralateral non-treated arthritic knees (N = 16).The synovial fluid was analyzed just before the first cold application, then 24 h later. IL-6, IL-1β, TNF-α, IL-17A,VEGF, NF-kB-p65 protein, and PG-E2 levels were measured in the synovial fluid and compared before/after thetwo cold applications.Results: Forty-seven patients were included (17 gouts, 11 calcium pyrophosphate deposition diseases, 13rheumatoid arthritides, 6 spondyloarthritides). Local ice cryotherapy significantly reduced the IL-6, IL-1β, VEGF,NF-kB-p65, and PG-E2 synovial levels, especially in the microcrystal-induced arthritis subgroup, while onlyphosphorylated NF-kB-p65 significantly decreased in rheumatoid arthritis and spondyloarthritis patients. ColdCO2 only reduced the synovial VEGF levels. In the phase II of the study, the synovial PG-E2 was significantlyreduced in ice-treated knees, while it significantly increased in the corresponding contralateral non-treatedarthritic knees, with a significant inter-class effect size (mean difference ? 1329 [? 2232; ? 426] pg/mL; N = 12).Conclusions: These results suggest that local ice cryotherapy reduces IL-6, IL-1β, and VEGF synovial proteinlevels, mainly in microcrystal-induced arthritis, and potentially through NF-kB and PG-E2-dependentmechanisms.