Interleukin-6 production and deregulation of the hypothalamic-pituitary-adrenal axis in patients with major depressive disorders

Abstract

The present study was designed to determine whether an association exists between HPA activity and cytokine production in major depression (MD). In 9 patients with MD and 11 control subjects of both sexes, all drug-free, activity of the HPA axis was evaluated by circadian rhythm of plasma cortisol, 24-h free urinary cortisol, an overnight 1 mg dexamethasone suppression test, and an oCRF stimulation test. Spontaneous and LPS-stimulated production of IL-1beta, IL-6, and TNFalpha by peripheral blood mononuclear cells were also determined. We found a significantly elevated spontaneous production of IL-6 in patients with MD (3541.2 +/- 726.8 vs 380.4 +/- 77.5 pg/mL in controls, p < 0.05), while LPS-stimulated production was significantly lower in patients than in control subjects (19,867.7 +/- 3649.2 vs 33,142.2 +/- 15,47.2 pg/mL, p < 0.05). The adrenocorticotropic hormone response to oCRF, evaluated as the area under the curve (AUCACTH) was significantly lower in patients than in control subjects (p = 0.02). A positive correlation between AUCACTH and LPS-stimulated IL-6 secretion was observed in patients with MD (r = 0.75, p < 0.05) but not in controls. These findings suggest that the activation of the inflammatory response described in depression might be associated with long-term hyperactivity of the HPA axis.