AB0080 Local Cryotherapy Decreases Arthritis Severity Via a Local Down-Regulation of Pro-Inflammatory Cytokines: A Study in Rat Adjuvant-Induced Arthritis
Authors: X. Guillot, H. Martin, C. Demougeot, D. Wendling, N. Tordi
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Local cryotherapy (LC) has been widely and empirically used in an adjuvant setting in rheumatic joint diseases. Unfortunately the promotion of the use of LC suffers from a low level of evidence of its benefits [1]. Moreover the mechanisms involved in its therapeutic effects in rheumatic diseases are not known. <h3>Objectives</h3> The first aim of this study was to investigate the effect of a chronic treatment with two types of cryotherapy (ice <i>versus</i> cold gas) on arthritic severity in adjuvant-induced arthritis (AIA) in rats. The second aim was to determine whether these effects rely on local anti-inflammatory effects. <h3>Methods</h3> Adjuvant-induced arthritis was induced in 6-week-old male Lewis rats by injecting <i>Mycobacterium Butyricum</i> and adjuvant in the tail. At the onset of arthritis (day 11), rats were treated either with local ice for 30 min (cages lined with ice pops, n=10) or with cold gas spray for 2 minutes on each hindpaw (n=9), twice a day for 14 consecutive days. Ten non-treated AIA rats served as controls. Arthritic score, tarsus diameter, body weight and skin temperatures after treatment were daily monitored. The day after the last cold application (day 24), hindpaws were processed to evaluate IL-6, IL-1β and TNF-α mRNA expression by quantitative PCR. <h3>Results</h3> As compared to controls, ice treatment significantly decreased mean arthritic scores and tarsus diameters from day 6 to day 14 (p&lt;0.001). Cold gas treatment induced a biphasic effect: it primarily worsened arthritis at days 11 and 12 (p&lt;0.01) and secondarily but tardily it decreased arthritis severity from day 21 to day 24 (p&lt;0.001). Body weights were unaffected by cryotherapy whatever the treatment. Likewise, skin temperatures were not different after ice or cold gas application. Both ice and cold gas treatments significantly decreased - to the same extent (-75%) - IL-6 and IL-1β mRNA hindpaw expressions as compared to non-treated rats (p&lt;0.001). By contrast, cryotherapy did not change TNF-α mRNA expression. IL-6, IL-1β mRNA hind paw expressions positively correlated with arthritic scores (r=0.6, p&lt;0.0001 and r=0.51, p&lt;0.0001, respectively). <h3>Conclusions</h3> Our results demonstrate for the first time the therapeutic and anti-inflammatory effects of local cryotherapy in adjuvant-induced arthritis, through direct down-regulation of IL-6 and IL-1β mRNA expression in arthritic paw tissues. Albeit chronic ice and cold gas application decrease local IL-6 and IL-1β levels to the same extent, the benefits of ice appeared earlier than those of cold spray. Our data give arguments to properly evaluate the effects of local cryotherapy in human arthritis. <h3>References</h3> Guillot X, Tordi N, Mourot L, Demougeot C, Dugué B, Prati C, Wendling D. Cryotherapy in inflammatory rheumatic diseases: a systematic review. Expert Rev Clin Immunol 2014 Feb;10(2):281-94. <h3>Disclosure of Interest</h3> None declared