Leukocyte glucocorticoid receptor expression and immunoregulation in veterans with and without post-traumatic stress disorder.
Post-traumatic stress disorder (PTSD) is associated with a dysregulation of the hypothalamus-pituitary-adrenal axis (HPA axis). In addition, there is evidence for altered glucocorticoid receptor (GR) expression and function in peripheral blood mononuclear cells. The aim of the present study was to differentiate between the effect of trauma exposure and PTSD on leukocyte GR expression and glucocorticoid immune regulation. Leukocyte GR binding characteristics and glucocorticoid sensitivity of immune activity, determined as the effect of dexamethasone (DEX) on in vitro cytokine release and T-cell proliferation, were compared between veterans with PTSD, traumatized veterans without PTSD and healthy controls. Leukocyte GR density was significantly lower in veterans with and without PTSD compared to healthy controls. DEX-induced inhibition of T-cell proliferation was significantly lower in PTSD compared to trauma and healthy controls. DEX-induced increase in lipopolysaccharide-stimulated interleukin-10 was less pronounced in traumatized veterans with and without PTSD compared to healthy controls. No group differences were observed in the effect of DEX on other cytokines or in baseline immune activity, except for lower tumor necrosis factor-alpha production in PTSD patients compared to healthy controls. The results suggest that trauma exposure is sufficient to induce changes in GR binding characteristics, whereas resistance of T-cell proliferation to DEX only occurs in PTSD. DEX resistance of in vitro immune activity was not a general phenomenon, but was restricted to specific immune functions.
de Kloet
C S
CS
Department of Military Psychiatry, Central Military Hospital, Utrecht, The Netherlands. c.s.dekloet@umcutrecht.nl
Vermetten
E
E
Bikker
A
A
Meulman
E
E
Geuze
E
E
Kavelaars
A
A
Westenberg
H G M
HG
Heijnen
C J
CJ
D000328:Adult; D000704:Analysis of Variance; D049109:Cell Proliferation; D003907:Dexamethasone / Q000378:metabolism; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012016:Reference Values; D013268:Stimulation, Chemical; D013313:Stress Disorders, Post-Traumatic / Q000276:immunology* / Q000378:metabolism; D013315:Stress, Psychological / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology; D014728:Veterans / Q000523:psychology
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D016753:Interleukin-10; D003907:Dexamethasone