Eur J Immunol. 2005 Oct 26;

Dehydroepiandrosterone replacement in patients with Addison's disease has a
bimodal effect on regulatory (CD4(+)CD25(hi) and CD4(+)FoxP3(+)) T cells.

Coles AJ, Thompson S, Cox AL, Curran S, Gurnell EM, Chatterjee VK.

Department of Clinical Neurosciences, University of Cambridge, Cambridge,
UK.

Oral replacement of the near-total deficiency of dehydroepiandrosterone
(DHEA) in patients with Addison's disease (adrenal insufficiency) enhances
mood and well-being and reduces fatigue. We studied the immunological
effects of 12 wk of oral DHEA treatment in ten patients with Addison's
disease receiving their normal mineralo- and glucocorticoid hormone
replacement. We found that baseline circulating regulatory T cells were
reduced in Addison's disease patients compared to controls, a hitherto
unrecognised defect in this disorder. Oral DHEA treatment had a bimodal
effect on naturally occurring regulatory (CD4(+)CD25(hi)FoxP3(+)) T cells
and lymphocyte FoxP3 expression. Oral DHEA replacement restored normal
levels of regulatory T cells and led to increased FoxP3 expression. These
effects were probably responsible for a suppression of constitutive
cytokine expression following DHEA withdrawal. In contrast, oral DHEA
treatment led to reduced FoxP3 expression induced by TCR engagement and so
augmented the cytokine response, but without a bias towards the Th1 or Th2
phenotype. NK and NKT cell numbers fell during DHEA treatment, and
homeostatic lymphocyte proliferation was increased. We conclude that DHEA
replacement in Addison's disease has significant immunomodulatory
properties and propose that it has a greater impact on the human immune
system than would be expected from its classification as a dietary
supplement.