BASIC AND TRANSLATIONAL RESEARCH

Acute cold stress in rheumatoid arthritis inadequately activates stress responses and induces an increase of interleukin 6

R H Straub¹, G Pongratz¹, H Hirvonen², T Pohjolainen³, M Mikkelsson², M Leirisalo-Repo⁴

¹ Laboratory of Experimental Rheumatology and Neuroendocrino-Immunology, Department of Internal Medicine I, University Hospital, Regensburg, Germany
² Rheumatism Foundation Hospital, Heinola, Finland
³ Orton, The Rehabilitation Unit of the Invalid Foundation, Helsinki, Finland
⁴ Department of Medicine, Division of Rheumatology, Helsinki University Central Hospital, Helsinki, Finland

ProfessorDr R H Straub, Laboratory of Experimental Rheumatology and Neuroendocrino-Immunology, Department of Internal Medicine I, University Hospital Regensburg, 93042 Regensburg, Germany; rainer.straub{at}klinik.uni-regensburg.de

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 –110°C and –60°C, and local cold therapy between –20°C and –30°C 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 –110°C cold stress followed by –60°C or local cold stress. The opposite was found in patients under GC therapy, in whom, unexpectedly, –110°C 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 –110°C 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.

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