Evidence for an association between an enhanced reactivity of interleukin-6 levels and reduced glucocorticoid sensitivity in patients with fibromyalgia

Pain and fatigue have been identified as core symptoms of fibromyalgia syndrome (FMS). Since both symptoms are also characteristic of hypocortisolemic disorders, reduced cortisol levels have been thought to promote an exacerbation of these FMS core symptoms by an enhanced reactivity of interleukin-6 (IL-6) levels. The aim of the current study was to investigate the pathophysiologic relevance of reduced cortisol levels for manifestation of FMS core symptoms. Twelve female FMS patients with 15 female controls were compared regarding the function of hypothalamus-pituitary-adrenal (HPA) axis and behavioral, endocrine and IL-6 responses after measuring the pressure pain thresholds (PPTs) at tender points. Function of HPA axis was assessed by determining the cortisol awakening response, daytime profile of cortisol secretion, low dose overnight dexamethasone suppression test (DST) and glucocorticoid sensitivity (GC) of inflammatory cytokine production. While endocrine and IL-6 responses were determined by collecting blood and saliva samples behavioral responses were assessed by pain and fatigue recordings of participants before and after PPT measurement using visual analogue scale (VAS). Whereas FMS patients were found not to differ from controls in cortisol awakening response, daytime profile of cortisol secretion and cortisol suppression after overnight DST, they did exhibit a reduced GC sensitivity of inflammatory cytokine production. PPT measurement did induce three times higher cortisol and four times higher IL-6 levels in FMS patients, but no change in their ACTH levels. The enhanced IL-6 reactivity after PPT measurement was accompanied by an increase in the severity of FMS patients' pain and fatigue ratings. The findings of the present study provide evidence for the pathophysiologic relevance of a disturbed glucocorticoid receptor (GR) function, rather than reduced cortisol levels for the maintenance of FMS core symptoms.