SAT0626 Local Cryotherapy (Pulsed CO2 or Ice) Decreases Il-6, IL-1β and VEGF Synovial Levels in Knee Arthritis
Authors: X. Guillot, N. Tordi, C. Laheurte, L. Pazart, C. Prati, P. Saas, D. Wendling
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Cryotherapy is widely and empirically used in an adjuvant and symptomatic setting in inflammatory rheumatic diseases, with a low level of evidence. <h3>Objectives</h3> The aim of this work was to evaluate the effects of two local cryotherapy (LC) techniques (ice or hyperbaric cold CO2) applied twice on pain and pro-inflammatory cytokine levels in arthritic knees. <h3>Methods</h3> Thirty-five patients suffering from non-septic knee arthritis were included (16 gouts, 8 calcium pyrophosphate dehydrate crystal deposition diseases, 5 spondyloarthritides, 6 rheumatoid arthritides). Patients didn9t receive any concurrent anti-inflammatory drug (corticosteroids, NSAIDs, colchicine, DMARDs, biologics) throughout the study period (24 hours). They were randomized to receive local ice (for 30 minutes) or cold pulsed CO2 (for 2 minutes - Cryo+® Cryonic) at 9 A.M and 5 P.M. Synovial fluid was collected just before the first cold application then 24 hours later (also at 9 A.M). Synovial fluid cell count and cytokine levels (IL-6, IL-1β, TNF-α, IL-17A, VEGF by Multiplex flow cytometry – CBA® BD biosciences) were measured and compared before and after the two LC applications. Paired Wilcoxon tests were performed. The factors associated with cytokine level evolution were assessed (uni- then multivariate analysis by logistic regression). <h3>Results</h3> Pain VAS significantly decreased after 24 hours in both treatment groups (Ice: 5.3±1.3 versus 2.7±1; n=20;p=0.0003 – CO2: 5.6±1.4 versus 3.1±1.2; n=15;p=0.002). Synovial fluid leukocyte count non-significantly decreased (23580±10015 versus 19120±8981; p=0.49). IL-6 levels significantly decreased after 2 LC applications 456100±163570pg/mL versus 281500±142006pg/mL; n=35; p=0.0001). This decrease was also significant in ice-treated subgroup (n=20; p=0.0002) but not in CO2-treated patients (n=15; p=0.07). In multivariate analysis, IL-6 decrease was associated with a higher CRP rate at baseline (r=0.35; p=0.004) and a greater skin temperature drop during LC (r=0.33; p=0.03). IL-1β levels also decreased after treatment (26.75±8.95pg/mL versus 23.10±10.11pg/mL; n=35; p=0.02) but the difference didn9t reach significance in treatment subgroups (Ice: n=19; p=0.07 – CO2: n=15; p=0.15). In multivariate analysis, IL-1β decrease was associated with "ice" modality (r=3.25; p=0.03) and negatively associated with BMI (r=-4.02; p=0.04). VEGF levels also decreased globally (1391±295pg/mL versus 1263±281pg/mL; n=34; p=0.03) but not significantly in subgroups (Ice: n=19; p=0.2 – CO2: n=15; p=0.07). IL-17A rates also tended to decrease (16.3±15.75pg/mL versus 14.95±15.2pg/mL; n=35; p=0.065). TNF-α levels tended to decrease in CO2 group (n=15; p=0.08). <h3>Conclusions</h3> LC (ice or pulsed CO2) applied twice during one day showed anti-inflammatory effects by reducing synovial IL-6, IL-1β and VEGF levels in arthritic knees. Both techniques equally reduced pain but sample sizes were still insufficient to show any difference in terms of local cytokine level reduction. <h3>Disclosure of Interest</h3> None declared