Functional disturbance of the stress-adaptation system in patients with scleroderma

Abstract

There have been several reports indicating the association between recent stress experiences and the onset or the exacerbation of rheumatic diseases, although few such reports exist in patients with scleroderma (SSc). The present study was performed to elucidate whether there were any functional disturbances in the neuro-endocrine-immune system as a homeostatic system upon stress in SSc patients. Various serum levels of stress-related hormones and cytokines were examined before and after a mental calculation stress test, and a basal questionnaire study of sense of coherence (SOC, which is related to the ability to cope with stress), recent stress experiences, and quality of life (QOL) was performed in 17 SSc patients and in 38 healthy volunteers. Physical QOL state was impaired in patients, but there were no differences in recent stress experiences and SOC scores between patients and controls. Basal serum cortisol levels were similar in patients and controls, but increased levels of proinflammatory cytokine and noradrenalin were seen in SSc patients. Characteristically, contrary to the control group, whose cortisol levels increased significantly following the mental calculation stress test, no significant increase was observed in the patients when post-test cortisol levels were compared to pre-test levels, suggesting a defect in the normal cortisol response upon stress in SSc patients. The present results suggest that there may be impaired function of the neuro-endocrine-immune system upon stress in SSc patients.

X chromosome gene methylation in peripheral lymphocytes from monozygotic twins discordant for scleroderma

“…While we can only speculate on the putative mechanisms justifying this association, we are traced back to earlier reports of the co-existence of phenylketonuriaassociated mental retardation and scleroderma [58]. Further, there are data suggesting that patients with SSc may have disturbances of the nervous system as represented by an impaired response to stress [59], the detection of central nervous system ischaemic vasculopathy at magnetic resonance imaging [60,61] and the changes in cerebrovascular reactivity [62].…”

Steroidogenesis in the skin: Implications for local immune functions

“…There is also predominance of Th17 and Th2 cells with release of IL-17, IL-4 and IL-13 at sites of lymphocytic infiltration which contributes to ongoing fibrosis [252]. Basal levels of cortisol, androstenedione, DHEA-S and 17-hydroxyprogesterone in patients with SSc do not differ from healthy controls [253, 254]. Levels of DHEA are lower and of ACTH are higher in SSc patients [254].…”

“…They also have a diminished response to a stress test or hypoglycemia, i.e. their level of cortisol does not increase [253, 254]. Apparently, the HPA axis malfunctions in these patients.…”

Mechanistic insight into the norepinephrine-induced fibrosis in systemic sclerosis

“…There have been a number of reports suggesting the possible involvement of stress and/or the stress-adaptation system in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus (SLE) 39 40 . It has also been reported that the serum NE levels are significantly higher in SSc patients than in normal individuals 1 . In addition, the mental stress-induced serum NE levels are also higher in SSc patients than in normal individuals based on mental calculation stress tests, suggesting that SSc patients may have an impaired function of the neuro-endocrine-immune system due to stress 1 .…”

“…NE is also synthesized in the locus coeruleus and adrenal medulla. It is well known that emotional stress and cold stimulation increase the systemic and/or local NE levels 1 2 3 . NE binds to the adrenergic receptor (AR) in multiple organs, including the heart, lungs, brain and skin.…”