HPA axis exhaustion and regulatory T cell accumulation in patients with a functional somatic syndrome: Recent view on the problem of Gulf War veterans

The authors proceeded from the assumption that physical and mental symptoms of functional somatic syndromes (including those observed in Gulf War veterans) are based on both underactivity of hypothalamic–pituitary–adrenal (HPA) axis and excessive accumulation of regulatory T cells (Tregs). Permanent psychogenic stress coupled with high antigen loading leads to gradual depletion of HPA axis, which is manifested by the reduction of stress-induced cortisol response. Under stress hormone deficiency, Tregs begin to play a principal role in anti-inflammatory mechanisms and each new pro-inflammatory stimulus increases their number. Superfluous accumulation of active Tregs results in malfunction of Th1 cells in the brain that leads to the appearance of neurodegeneration foci, which seems to be an anatomic substance for various cognitive and psychological symptoms. New approaches to the treatment of such conditions are also discussed.