Glucocorticoid sensitivity of immune cells in severely fatigued adolescent girls: a longitudinal study.

Fatigue during adolescence is associated with somatic and psychological complaints that resemble the pattern of symptoms described for chronic fatigue syndrome (CFS). Studies in CFS and other stress-related syndromes suggested a dysfunction of the interactions between the hypothalamic-pituitary-adrenal axis (HPA-axis) and the immune system, i.e. a changed glucocorticoid (GC) receptor sensitivity of immune cells, to exist. Here we investigated whether severely fatigued girls from a healthy population have altered cortisol production and immune cell sensitivity for the synthetic GC, dexamethasone (DEX). In a longitudinal design, we examined ex vivo DEX sensitivity of monocytes and of T-cell mitogen-induced responses of severely fatigued (N=65) and non-fatigued girls (N=60). Fatigued girls reported more severe comorbid complaints than non-fatigued participants across three measurements during 1 year (T1: spring, T2: autumn, T3: spring) and had higher plasma cortisol levels throughout the study. DEX sensitivity of T-cell mitogen-induced responses showed seasonal variation with increased sensitivity in autumn compared to spring. No systematic variation of monocyte glucocorticoid receptor (GR) sensitivity was observed. Significant rank correlations of DEX sensitivity of T-cell mitogen-induced responses between the three assessments during the year suggest a stable trait of immune function. Groups did not differ in DEX sensitivity on any of the read outs. However, in a persistently fatigued subgroup, sensitivity to DEX was significantly reduced on the level of interferon (IFN)-gamma production. These results show that although fatigued participants had severe (comorbid) complaints, only in the case when symptoms persisted, altered GC sensitivity of immune cells was observed.