Effects of dexamethasone on cytokine plasma levels and white blood cell counts in depressed patients.
In major depression, alterations of some aspects of the host defense system and the hypothalamo-pituitary-adrenal (HPA) system have been reported. Both systems are closely related, but their interaction in major depression has not yet been explored. Moreover, little is known about the effects of glucocorticoids on the circulating amounts of cytokines in humans in the absence of immunological challenges. Therefore, we investigated the effects of dexamethasone (DEX) in 17 depressed patients who underwent a combined DEX-suppression and corticotropine-releasing-hormone (CRH)-stimulation test on white blood cell counts, and on the plasma levels of granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-alpha, and soluble TNF-receptors (sTNF-R) p55 and p75. DEX induced an increase in granulocyte counts, which was positively correlated with increases in the circulating amounts of G-CSF and paralleled by decreased lymphocyte and monocyte counts. Moreover, DEX reduced the plasma levels of IL-6, TNF-alpha and sTNF-R p75. The levels of sTNF-R p55 and IL-10 were not affected. DEX-induced changes in immunological parameters did not differ between patients who had different amounts of HPA-system alteration, and were neither related to the severity of depressive symptomatology or to other clinical features. We conclude that a single oral dose of DEX, even in the absence of infection and inflammation, affects the circulating amounts of cytokines and soluble cytokine receptors, further supporting the pivotal role of these immune-mediators in glucocorticoid-induced immunomodulation. Neuroendocrinological alterations associated with major depression seem to be independent from these processes.
Schuld
A
A
Max Planck Institute of Psychiatry, Kraepelinstrasse 10, D-80804, Munich, Germany. schuld@mpipsykl.mpg.de
Kraus
T
T
Haack
M
M
Hinze-Selch
D
D
Zobel
A W
AW
Holsboer
F
F
Pollmächer
T
T
D000311:Adrenal Glands / Q000187:drug effects / Q000503:physiopathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003346:Corticotropin-Releasing Hormone; D016207:Cytokines / Q000097:blood*; D003863:Depression / Q000097:blood / Q000276:immunology*; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology; D007109:Immunity / Q000187:drug effects; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D016207:Cytokines; D005938:Glucocorticoids; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D016179:Granulocyte Colony-Stimulating Factor; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone