Hypocortisolism and increased glucocorticoid sensitivity of pro-Inflammatory cytokine production in Bosnian war refugees with posttraumatic stress disorder.
BACKGROUND
Posttraumatic stress disorder (PTSD) is associated with dysregulation of the hypothalamus pituitary adrenal (HPA) axis. Alterations include various responses to HPA axis stimulation, different basal hormone levels, and changes in glucocorticoid receptor (GR) numbers on lymphocytes. The functional significance of these latter changes remains elusive.


METHODS
Twelve Bosnian war refugees with PTSD and 13 control subjects were studied. On 2 consecutive days, they collected saliva samples after awakening and at 11, 15, and 20 hours. Glucocorticoid (GC) sensitivity was measured by dexamethasone (DEX) inhibition of lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) production in whole blood.


RESULTS
The PTSD patients showed no cortisol response after awakening and had lower daytime cortisol levels (F = 14.57, p <.001). Less DEX was required for cytokine suppression in PTSD patients (IL-6: t = -2.82, p =.01; TNF-alpha: t = 5.03, p <.001), reflecting higher GC sensitivity of pro-inflammatory cytokine production. The LPS-stimulated production of IL-6, but not TNF-alpha, was markedly increased in patients (IL-6: F = 10.01, p <.004; TNF-alpha: F =.89, p =.34).


CONCLUSIONS
In refugees with PTSD, hypocortisolism is associated with increased GC sensitivity of immunologic tissues. Whether this pattern reflects an adaptive mechanism and whether this is sufficient to protect from detrimental effects of low cortisol remains to be investigated.
Rohleder
Nicolas
N
Department of Psychology, Institute of Experimental Psychology II, University of Düsseldorf, Düsseldorf, Germany.
Joksimovic
Ljiljana
L
Wolf
Jutta M
JM
Kirschbaum
Clemens
C
D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents; D017522:Bosnia and Herzegovina / Q000208:ethnology; D003907:Dexamethasone; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D005858:Germany; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D015848:Interleukin-5 / Q000097:blood*; D008070:Lipopolysaccharides / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D012036:Refugees / Q000523:psychology*; D013313:Stress Disorders, Post-Traumatic / Q000276:immunology* / Q000523:psychology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014857:Warfare
D000893:Anti-Inflammatory Agents; D015848:Interleukin-5; D008070:Lipopolysaccharides; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D006854:Hydrocortisone