Multiple Reciprocal Relationships Between in Vivo Cellular Immunity and Hypothalamic—Pituitary—Adrenal Axis in Depression

Major depression is reportedly characterized by increased activity of the hypothalamic- pituitary-adrenal (HPA) axis and by in vivo immune activation. The present study was carried out in order to investigate the relationships between HPA-axis activity and in vivo immune function in depression. Towards this end the following parameters were measured: 24 h urinary cortisol (UC) excretion; basal and post-dexamethasone (DST) plasma cortisol, β-endorphin/β-lipotropin (βEND/βLPH) and dexamethasone concentrations; and leucocyte subsets (i.e. lymphocytes, neutrophils, monocytes, CD4⁺, CD4⁺CD45RA⁺, CD4⁺CD45RO⁺, CD8⁺, CD8⁺CD57⁺, CD8⁺CD57^-, HLA-DR⁺, CD25⁺ T cells, HLA-DR⁺, CD19⁺, CD20+, and CD21+ B cells) both pre-and post-DST. Dexamethasone administration (1 mg orally) induced leucocytosis, lymphocytopaenia, monocytopaenia and neutrophilia. HPA-axis non-suppressors exhibited a relative resistance to the enhancing (e.g. neutrophils) or depressant (e.g. lymphocytes, CD4⁺ T cells) effects of dexamethasone. There were significant correlations between UC excretion and the number of percentage of lymphocytes, monocytes, CD4⁺CD45RA⁺ and CD8⁺CD57^-T cells (negatively) and neutrophils (positively). It is concluded that multiple and complex intertwined relationships between HPA-axis hyperactivity and systemic immune stimulation participate in the pathophysiology or pathogenesis of major depression.