Published in:
Open Access 01-12-2019 | Arthritis | Research article
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
Published in: Arthritis Research & Therapy | Issue 1/2019
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Background
The aim of this study was to assess the anti-inflammatory effects of local cryotherapy in human non-septic knee 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-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 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 the two cold applications.
Results
Forty-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-1β, 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).
Conclusions
These results suggest that local ice cryotherapy reduces IL-6, IL-1β, and VEGF synovial protein levels, mainly in microcrystal-induced arthritis, and potentially through NF-kB and PG-E2-dependent mechanisms.
Trial registration
Clinicaltrials.gov, NCT03850392—registered February 20, 2019—retrospectively registered