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Acute Cold Stress in Rheumatoid Arthritis Inadequately Activates Stress Responses and Induces an Increase of Interleukin 6

R H Straub, G Pongratz, H Hirvonen, T Pohjolainen, M Mikkelsson, M LeirisaloRepo4


ABSTRACT

Objective: Acute stress in patients with rheumatoid arthritis (RA) should stimulate a strong stress response. After cryotherapy, we expected to observe an increase of hormones of the adrenal gland and the sympathetic nervous system.

Methods: A total of 55 patients with RA were recruited for whole-body cryotherapy at 2110uC and 260uC, and local cold therapy between 220uC and 230uC for 7 days. We measured plasma levels of steroid hormones, neuropeptide Y (sympathetic marker), and interleukin (IL)6 daily before and after cryotherapy.

Results: In both therapy groups with/without glucocorticoids (GC), hormone and IL6 levels at baseline and 5 h after cold stress did not change over 7 days of cryotherapy. In patients without GC, plasma levels of cortisol and androstenedione were highest after 2110uC cold stress followed by 260uC or local cold stress. The opposite was found in patients under GC therapy, in whom, unexpectedly, 2110uC cold stress elicited the smallest responses. In patients without GC, adrenal cortisol production increased relative to other adrenal steroids, and again the opposite was seen under GC therapy with a loss of cortisol and an increase of dehydroepiandrosterone. Importantly, there was no sympathetic stress response in both groups. Patients without GC and 2110uC cold stress demonstrated higher plasma IL6 compared to the other treatment groups (not observed under GC), but they showed the best clinical response.

Conclusions: We detected an inadequate stress response in patients with GC. It is further shown that the sympathetic stress response was inadequate in patients with/without GC. Paradoxically, plasma levels of IL6 increased under strong cold stress in patients without GC. These findings confirm dysfunctional stress axes in RA.