Estrogen modulates the hypothalamic-pituitary-adrenal and inflammatory cytokine responses to endotoxin in women

Details

Serval ID
serval:BIB_FEEF330F1FE8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Estrogen modulates the hypothalamic-pituitary-adrenal and inflammatory cytokine responses to endotoxin in women
Journal
Journal of Clinical Endocrinology and Metabolism
Author(s)
Puder  J. J., Freda  P. U., Goland  R. S., Wardlaw  S. L.
ISSN
0021-972X
Publication state
Published
Issued date
06/2001
Peer-reviewed
Oui
Volume
86
Number
6
Pages
2403-8
Notes
Journal Article
Research Support, U.S. Gov't, P.H.S. --- Old month value: Jun
Abstract
Endotoxin stimulates the release of the inflammatory cytokines interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-alpha, which are potent activators of the hypothalamic-pituitary-adrenal (HPA) axis. Recent studies in the rodent and in the primate have shown that the HPA responses to endotoxin and IL-1 were enhanced by gonadectomy and attenuated by estradiol (E2) replacement. In addition, there is some evidence, in the rodent, that estrogen modulates inflammatory cytokine responses to endotoxin. To determine whether estrogen has similar effects in humans, we studied the cytokine and HPA responses to a low dose of endotoxin (2--3 ng/kg) in six postmenopausal women with and without transdermal E2 (0.1 mg) replacement. Mean E2 levels were 7.3 +/- 0.8 pg/mL in the unreplaced subjects and increased to 102 +/- 13 pg/mL after estrogen replacement. Blood was sampled every 20 min for 1--2 h before, and for 7 h after, iv endotoxin administration. Endotoxin stimulated ACTH, cortisol, and cytokine release in women with and without E2 replacement. E2 significantly attenuated the release of ACTH (P < 0.0001) and of cortisol (P = 0.02). Mean ACTH levels peaked at 190 +/- 91 pg/mL in the E2-replaced group vs. 411 +/- 144 pg/mL in the unreplaced women, whereas the corresponding mean cortisol levels peaked at 27 +/- 2.9 microg/dL with E2 vs. 31 +/- 3.2 microg/dL without E2. Estrogen also attenuated the endotoxin-induced release of IL-6 (P = 0.02), IL-1 receptor antagonist (P = 0.003), and TNF-alpha (P = 0.04). Mean cytokine levels with and without E2 replacement peaked at 341 +/- 94 pg/mL vs. 936 +/- 620 pg/mL for IL-6, 82 +/- 14 ng/mL vs. 133 +/- 24 ng/mL for IL-1 receptor antagonist, and 77 +/- 46 pg/mL vs. 214 +/- 87 pg/mL for TNF-alpha, respectively. We conclude that inflammatory cytokine and HPA responses to a low dose of endotoxin are attenuated in postmenopausal women receiving E2 replacement. These data show, for the first time in the human, that a physiological dose of estrogen can restrain cytokine and neuroendocrine responses to an inflammatory challenge.
Keywords
Adrenocorticotropic Hormone/blood Adult Aged Endotoxins/*pharmacology Estradiol/*therapeutic use Female Humans Hydrocortisone/blood Hypothalamo-Hypophyseal System/*drug effects Interleukin 1 Receptor Antagonist Protein Interleukin-6/*blood Middle Aged Pituitary-Adrenal System/*drug effects Postmenopause/blood Sialoglycoproteins/*blood Tumor Necrosis Factor-alpha/*metabolism
Pubmed
Web of science
Create date
15/02/2008 18:19
Last modification date
20/08/2019 17:29
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