Background In several studies an effect of whole-body cryotherapy (WBCT) on pain relief and reduction of inflammatory symptoms has been demonstrated and it is recommended for the treatment of arthritis, fibromyalgia and ankylosing spondylitis. The mode of action of this therapy, which consists in a brief exposure to temperatures between -110 and -160°C in special cryochambers, has not been fully elucidated.
Objectives The aim of this study was to investigate the changes in the gene expression of selected genes (CCL4, TGFBR3, CD69 and MAP2K3) identified as significantly regulated in a small pilot study using Affymetrix GeneChip® Human Gene 1.0 ST arrays in cells from peripheral blood of patients with fibromyalgia going through a series of three exposures to WBCT within three days.
Methods Twenty two patients with fibromyalgia (20 female/2 male, age 51.7±8.9 years (mean ± SD) were included in the study and underwent 3 exposures to WBCT in a cryochamber system with 3 chambers (10 seconds at -10°C, 10 seconds at -60°C and for maximum 3 minutes at -110°C) at 3 consecutive days. During the study patients did not change their medication. Blood was collected immediately prior to (baseline) and directly after the first exposure to WBCT and after the third exposure using PAXgene™ RNA tubes. Total RNA was extracted with the PAXgene Blood RNA kit. Gene expression levels of MAP2K3, CCL4, TGFBR3, and CD69 were analysed by real-time PCR using sequence-specific primers and probes (TaqMan).
Results All 22 patients tolerated the application of the WBCT well and reported to benefit from this treatment. The expression levels of CCL4 in cells from peripheral blood reduced significantly to mean 67% in 19 of 22 patients after the third exposure compared to baseline. The expression level of CD69 was also reduced in the majority of patients (16 out of 22) significantly to 59%. In contrast, the expression of MAP2K3 was found to be up-regulated in 13 patients to mean 180%, while the expression levels in the other nine patients remained almost unchanged. The changes of gene expression levels observed after the third exposure compared to baseline became apparent already after the first cold exposure, without reaching statistical significance. The down-regulation of TGFBR3 observed in the pilot study could not be confirmed in the larger cohort.
Conclusions The results of our study indicate, that the whole-body cryotherapy may cause significant changes in gene expression levels of CCL4, CD69 and MAP2K3. The MAP2K3 expression is known to be regulated by environmental stress, which is in accordance with the observed up-regulation of MAP2K3 expression. The down-regulation of the CD69, a marker for T-cell activation and the chemokine CCL4 that is produced by T-cells indicate that the exposure to WBCT has an effect on peripheral T-cells. Whether this influence on T-cells contributes to the therapeutic effect needs to be elucidated.
Disclosure of Interest None declared
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