Document Detail


Role of glucocorticoids in the response of the hypothalamo-corticotrope, immune and adipose systems to repeated endotoxin administration.
MedLine Citation:
PMID:  10343177     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
T Chautard; E Spinedi; M Voirol; F P Pralong; R C Gaillard
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neuroendocrinology     Volume:  69     ISSN:  0028-3835     ISO Abbreviation:  Neuroendocrinology     Publication Date:  1999 May 
Date Detail:
Created Date:  2000-04-13     Completed Date:  2000-04-13     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0035665     Medline TA:  Neuroendocrinology     Country:  SWITZERLAND    
Other Details:
Languages:  eng     Pagination:  360-9     Citation Subset:  IM    
Affiliation:
Division of Endocrinology, University Hospital (CHUV), Lausanne, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
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
Chemical
Reg. No./Substance:
0/Cytokines; 0/Drug Implants; 0/Endotoxins; 0/Glucocorticoids; 0/Leptin; 0/Lipopolysaccharides; 0/Tumor Necrosis Factor-alpha; 50-22-6/Corticosterone; 9002-60-2/Adrenocorticotropic Hormone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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