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

Ann Rheum Dis. 2009 Apr;68(4):572-8. doi: 10.1136/ard.2008.089458. Epub 2008 Apr 15.

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

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstenedione / blood
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / therapy
  • Biomarkers / blood
  • Cryotherapy / methods*
  • Dehydroepiandrosterone / blood
  • Female
  • Glucocorticoids / therapeutic use
  • Humans
  • Hydrocortisone / blood
  • Interleukin-6 / blood*
  • Male
  • Middle Aged
  • Neuropeptide Y / blood
  • Statistics, Nonparametric
  • Stress, Physiological*

Substances

  • Biomarkers
  • Glucocorticoids
  • Interleukin-6
  • Neuropeptide Y
  • Androstenedione
  • Dehydroepiandrosterone
  • Hydrocortisone