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Acute cold stress in rheumatoid arthritis inadequately activates stress responses and induces an increase of interleukin-6
  1. Rainer H Straub (rainer.straub{at}
  1. University Hospital Regensburg, Germany
    1. Georg Pongratz (georg.pongratz{at}
    1. University Hospital Regensburg, Germany
      1. Hanna Hirvonen (hanna.hirvonen{at}
      1. Rheumatism Foundation Hospital, Heinola, Finland
        1. Timo Pohjolainen
        1. Orton, the Rehabilitation Unit of the Invalid Foundation, Helsinki, Finland
          1. Marja Mikkelsson (marja.mikkelsson{at}
          1. Rheumatism Foundation Hospital, Heinola, Finland
            1. Marjatta Leirisalo-Repo (marjatta.leirisalo-repo{at}
            1. Helsinki University Central Hospital, Finland


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

              Methods: Fifty-five 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 7d. We measured plasma levels of steroid hormones, neuropeptide Y (sympathetic marker), and IL-6 daily before and after cryotherapy.

              Results: In both therapy groups with/without glucocorticoids (GC), hormone and IL-6 levels at baseline and 5hr after cold stress did not change during 7d 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. This was opposite 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, which was again opposite under GC therapy with a loss of cortisol and an increase of DHEA. Importantly, there was no sympathetic stress response in both groups. Patients without GC and 110°C cold stress demonstrated higher plasma IL-6 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 IL-6 increased under strong cold stress in patients without GC. These findings confirm dysfunctional stress axes in RA.

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