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AB0083 Local ice cryotherapy decreases prostaglandin-e2, nf-kb and il-6 synovial levels in arthritic knees compared to contralateral non-treated joints
  1. X. Guillot1,2,3,
  2. N. Tordi2,
  3. C. Laheurte4,
  4. L. Pazart5,
  5. C. Prati2,3,
  6. P. Saas4,
  7. D. Wendling3,6
  1. 1Rheumatology Department, Felix Guyon University Hospital, Saint-Denis, Réunion
  2. 2PEPITE EA4267, FHU Increase, Bourgogne-Franche-Comté University
  3. 3Rheumatology Department
  4. 4INSERM U1098, Biomonitoring Platform, EFS
  5. 5CIC IT, INSERM Center CIT 808, Besançon University Hospital
  6. 6EA 4266, Bourgogne-Franche-Comté university, Besançon, France


Background Cryotherapy is widely used in rheumatic diseases, with a low level of evidence. Tissue mild hypothermia was reported to inhibit pivotal pro-inflammatory enzyme pathways such as COX-2/PG-E21 and NF-kB.2

Objectives We hypothesised that local cryotherapy (LC) might reduce joint inflammation through PG-E2 and NF-kB repression.

Methods 47 patients suffering from non-septic knee arthritis were included (17 gouts, 11 calcium pyrophosphate dehydrate crystal deposition diseases, 6 spondyloarthritides, 13 rheumatoid arthritides), taking no concurrent anti-inflammatory drug/DMARD. They were first randomised to receive local ice (30 min-N=16) or cold pulsed CO2 (2 min – Cryo+ Cryonic-N=16) at 9 A.M and 5 P.M. Synovial fluid was collected just before the first cold application then 24 hours later (9 A.M). Synovial fluid IL-6, IL-1β, TNF-α, IL-17A, VEGF (Multiplex flow cytometry), NF-kB P65 (total/phosphorylated) and PG-E2 (ELISA) were measured and compared before and after 2 LC applications. Contralateral non-treated knees were then used as paired controls (in 16 other ice-treated patients).

Results Synovial IL-6 significantly decreased after 2 LC applications (n=43 paired Wilcoxon:p=0.00015). This decrease was also significant in ice-treated subgroup (n=16 p<0.005) but not in CO2-treated patients (n=14;p=0.1). IL-1β and VEGF levels also decreased after treatment (n=44-p=0.02 and n=47-p=0.03) but not significantly in treatment subgroups. By contrast, IL-6 (n=13), IL-1β (n=15) and VEGF (n=15) didn’t change in contralateral non-treated knees. LC had no significant effect on IL-17A nor TNF-α synovial levels. LC significantly reduced synovial NF-kB (n=38-p=0.04) and NF-kB-P levels (n=38-p=0.004). These levels were also significantly decreased in ice-treated patients (n=26-p=0.03 and 0.003) but not in CO2-treated patients (n=13). We observed no effect on the NF-kB levels in contralateral non-treated knees (n=12). NF-kB variations correlated significantly with IL-6 (Pearson’s r=0.48-N=32 p<0.01) and VEGF (r=0.34-N=36-p=0.038) variations, and with the maximal skin temperature drop induced by LC (r=0.32-N=36-p=0.047). LC significantly reduced synovial PG-E2 (n=38-p=0.04), which was also significantly decreased in ice-treated patients (n=26-p=0.02) but not in CO2-treated patients (n=13). Conversely, we observed a significant increase in PG-E2 levels in contralateral non-treated knees (n=12-p=0.04), with a significant inter-class effect-size (weighted mean difference −1329 [−2232;−426] pg/mL-in 12 bi-arthritic patients).

Conclusions Local ice cryotherapy applied twice during one day showed superior anti-inflammatory effects compared to local CO2, notably by reducing synovial IL-6 levels in arthritic knees. We also showed for the first time that this inhibitory effect on cytokine levels might be PG-E2 and NF-kB dependent, notably through significant inhibitory effects on the PG-E2 and (to a lesser extent) NF-kB pathways.

References [1] Diestel. Cryobiology2008.

[2] Yenari. Neurochem Int2006.

Disclosure of Interest None declared

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