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

BackgroundThe aim of this study was to assess the anti-inflammatory effects of local cryotherapy in human non-septic knee arthritis.MethodsIn the phase I of the study, patients were randomized to receive either ice (30min; N=16) or cold CO2 (2min; N=16) applied twice during 1day at an 8-h interval on the arthritic knee. In phase II, 16 other ice-treated arthritic 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 24h later. IL-6, IL-1 beta, TNF-alpha, IL-17A, VEGF, NF-kB-p65 protein, and PG-E2 levels were measured in the synovial fluid and compared before/after the two cold applications.ResultsForty-seven patients were included (17 gouts, 11 calcium pyrophosphate deposition diseases, 13 rheumatoid arthritides, 6 spondyloarthritides). Local ice cryotherapy significantly reduced the IL-6, IL-1 beta, VEGF, NF-kB-p65, and PG-E2 synovial levels, especially in the microcrystal-induced arthritis subgroup, while only phosphorylated NF-kB-p65 significantly decreased in rheumatoid arthritis and spondyloarthritis patients. Cold CO2 only reduced the synovial VEGF levels. In the phase II of the study, the synovial PG-E2 was significantly reduced in ice-treated knees, while it significantly increased in the corresponding contralateral non-treated arthritic knees, with a significant inter-class effect size (mean difference -1329 [-2232; -426] pg/mL; N=12).ConclusionsThese results suggest that local ice cryotherapy reduces IL-6, IL-1 beta, and VEGF synovial protein levels, mainly in microcrystal-induced arthritis, and potentially through NF-kB and PG-E2-dependent mechanisms.Trial registrationClinicaltrials.gov, NCT03850392-registered February 20, 2019-retrospectively registered