Role of glucocorticoids in the response of the hypothalamo-corticotrope, immune and adipose systems to repeated endotoxin administration

Détails

ID Serval
serval:BIB_BE3BD42C57F1
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Role of glucocorticoids in the response of the hypothalamo-corticotrope, immune and adipose systems to repeated endotoxin administration
Périodique
Neuroendocrinology
Auteur(s)
Chautard  T., Spinedi  E., Voirol  M., Pralong  F. P., Gaillard  R. C.
ISSN
0028-3835 (Print)
Statut éditorial
Publié
Date de publication
05/1999
Volume
69
Numéro
5
Pages
360-9
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: May
Résumé
The present study was designed to determine whether the glucocorticoid inhibitory feedback mechanism plays a role in the well-known tolerance of the neuroendocrine-immune axis response to repeated endotoxemia. Adult male rats underwent adrenalectomy (ADX) and were implanted with a subcutaneous corticosterone (compound B, CB, 75 mg) pellet, or sham operated and implanted with a placebo pellet. On the morning of day 8 after surgery (experimental day, D1), all rats received an intravenous injection of lipopolysaccharide (LPS) (25 microg/kg body weight) which was repeated daily until D5. Blood was drawn via intravenous indwelling catheters before (sample time zero) as well as 1, 2, 3 and 4 h after LPS treatment on D1, 3 and 5 for measurements of corticotropin (ACTH), CB, tumor necrosis factor-alpha (TNF-alpha) and leptin. In sham animals, tolerance to repeated LPS administration was complete by D5 for the corticotrope axis and the immune response. In addition, LPS was found to stimulate leptin secretion on day 1 in intact rats, an effect that also disappeared thereafter. ADX + CB rats showed only a partial tolerance of the corticotrope axis on D5, whereas tolerance of the immune response was similar to that found in sham animals. Interestingly, the acute stimulation of leptin secretion by LPS in ADX + CB rats was qualitatively similar to that of intact controls on D1, but plasma leptin levels were significantly reduced on D3 and 5 compared to controls. Our results demonstrate that the adrenal response tolerance of the hypothalamo-pituitary-adrenal axis to repeated endotoxemia. In addition, our finding that TNF-alpha secretion follows the same pattern in sham-operated and in adrenalectomized animals suggests that unlike the corticotrope axis, tolerance of the immune response does not depend upon stimulated CB levels. The decrease in circulating levels of leptin following ADX is consistent with the stimulatory effects of glucocorticoids on leptin secretion. However, our finding of an acute stimulation of leptin secretion by LPS in ADX + CB animals demonstrates that this effect of endotoxemia is at least partially glucocorticoid independent.
Mots-clé
Adipose Tissue/*physiopathology Adrenalectomy Adrenocorticotropic Hormone/blood/*physiology Animals Body Weight/drug effects Corticosterone/administration & dosage/pharmacology Cytokines/blood Dose-Response Relationship, Drug Drug Implants Electroshock Endotoxins/*pharmacology Glucocorticoids/*physiology Hypothalamo-Hypophyseal System/*drug effects/physiology Immune System/*physiopathology Leptin/blood Lipopolysaccharides/toxicity Male Rats Rats, Wistar Tumor Necrosis Factor-alpha/metabolism
Pubmed
Web of science
Création de la notice
25/01/2008 17:26
Dernière modification de la notice
20/08/2019 16:32
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