Cytokine inhibition after glucocorticoid exposure in healthy men with low versus high basal cortisol levels.
OBJECTIVE
The balance between glucocorticoid (GC) release and GC sensitivity in target cells is believed to be important to maintain homeostasis in the neuroendocrine control of inflammation. We investigated the impact of in vivo exposure to adrenocorticotropic hormone (ACTH) and dexamethasone (DEX) on GC sensitivity measured in vitro in healthy individuals with high versus low baseline cortisol levels.


METHODS
136 healthy male volunteers were screened twice and sorted according to their 24-hour urinary free cortisol (UFC) excretion. The 10 individuals with the highest UFC (290 +/- 87 nmol/24 h) and the 10 with the lowest UFC (168 +/- 34 nmol/24 h) were further tested. Measurements were performed at baseline, after a low dose (0.5 microg/1.73 m(2)) of ACTH challenge and after 2 weeks' exposure to DEX (0.1 mg twice daily). GC sensitivity was assessed in vitro as the ability of DEX to inhibit lipopolysaccharide-stimulated production of the cytokines interleukin 1-beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in a whole-blood assay.


RESULTS
After exposure to DEX in vivo, inhibition of IL-6 and TNF-alpha decreased. Also, after DEX in vivo, low-cortisol men showed lower inhibition of IL-1beta and IL-6, both compared to the high-cortisol group and their own baseline levels.


CONCLUSIONS
A downregulation of GC sensitivity in leukocytes after exposure to an exogenous GC seems to occur most strongly in men with low cortisol levels.
Lekander
Mats
M
Department of Clinical Neuroscience, Section of Psychology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. Mats.Lekander@ki.se
Axén
Jennie
J
Knutsson
Urban
U
Olgart Hoglund
Caroline
C
Werner
Sigbritt
S
Wikstrom
Ann-Charlotte
AC
Stierna
Pontus
P
D000324:Adrenocorticotropic Hormone / Q000378:metabolism / Q000494:pharmacology; D000328:Adult; D016207:Cytokines / Q000097:blood*; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis / Q000097:blood*; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D007249:Inflammation / Q000097:blood* / Q000276:immunology* / Q000503:physiopathology; D015850:Interleukin-6 / Q000097:blood; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D009490:Neurosecretory Systems / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D013315:Stress, Psychological / Q000097:blood / Q000276:immunology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D016207:Cytokines; D005938:Glucocorticoids; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone