Patients with rheumatoid arthritis (RA) mount an inadequate response to acute cold stress, particularly when receiving glucocorticoid (GC) treatment, research suggests.
“The hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS) have been shown to be vulnerable in patients with RA,” note Rainer Straub (University Hospital Regensburg, Germany) and colleagues.
“A defect of stress axes may lead to unwanted pro-inflammatory side effects,” they add.
To investigate the role of cold stress on the HPA axis and the SNS, Straub and team measured plasma levels of steroid hormones, neuropeptide Y (a sympathetic marker), and interleukin (IL)-6 before and after whole-body cryotherapy at –110°C and –60°C, and local cold therapy between –20°C and –30°C in 55 patients with RA.
Since GC treatment can change hormonal and neuronal responses, the researchers separated the patients according to ongoing treatment.
The researchers found that hormone and IL-6 levels at baseline and 5 hours after cold stress did not change over 7 consecutive days of cryotherapy, regardless of whether the patients were receiving GC treatment or not.
In patients not receiving 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 who, unexpectedly, -110°C cold stress elicited the smallest responses, with the adrenal cortisol response being particularly weak.
Adrenal cortisol production increased relative to other adrenal steroids in patients not receiving GC. Again, the opposite was true under GC therapy with a loss of cortisol and an increase of dehydroepiandrosterone observed by the researchers.
“Under cold stress, a typical increase of the activity of the SNS is expected,” say Straub and co-authors in the Annals of Rheumatic Diseases. However, in this study, there was no sympathetic stress response in either group.
Interestingly, patients not receiving GC who underwent –110°C cold stress had the highest plasma IL-6 levels of all the groups but also showed the best clinical response.
“This indicates that –110°C cold stress is different with respect to the beneficial effect compared to -60°C or local cold stress,” remark the researchers.
They conclude: “These findings confirm dysfunctional stress axes in RA.”