Biological and diurnal variation in glucocorticoid sensitivity detected with a sensitive in vitro dexamethasone suppression of cytokine production assay

Cardinal, John, Pretorius, Carel J. and Ungerer, Jacobus P. J. (2010) Biological and diurnal variation in glucocorticoid sensitivity detected with a sensitive in vitro dexamethasone suppression of cytokine production assay. Journal of Clinical Endocrinology and Metabolism, 95 8: 3657-3663.


Author Cardinal, John
Pretorius, Carel J.
Ungerer, Jacobus P. J.
Title Biological and diurnal variation in glucocorticoid sensitivity detected with a sensitive in vitro dexamethasone suppression of cytokine production assay
Formatted title Biological and diurnal variation in glucocorticoid sensitivity detected with a sensitive in vitro dexamethasone suppression of cytokine production assay
Journal name Journal of Clinical Endocrinology and Metabolism  (ERA 2012 Listed)    (ERA 2010 Rank A*)   Check publisher's open access policy
Publication date 2010-08-01
Sub-type Article
DOI 10.1210/jc.2009-2720
Volume number 95
Issue number 8
ISSN 0021-972X; 1945-7197
Start page 3657
End page 3663
Total pages 7
Place of publication Chevy Chase, MD, United States
Publisher The Endocrine Society
Language eng
Formatted abstract Introduction: Glucocorticoid resistance due to mutations of the glucocorticoid receptor (NR3C1) are rare, but reduced glucocorticoid sensitivity may play a role in steroid-resistant asthma, inflammatory bowel disease, and septic shock. A rapid and sensitive functional assay to detect glucocorticoid resistance will be advantageous.
Method: We describe a rapid in vitro monocyte dexamethasone suppression of cytokine production (DSCP) assay with a 3-h incubation. The DSCP assay was compared with the reference stimulated lymphocyte proliferation method. We characterized the effect of delayed processing, time of sampling, and biological variation on the DSCP assay.
Results: The DSCP assay clearly distinguished subjects with a known heterozygous mutation of the NR3C1 gene from control subjects, whereas the reference method failed. Decreased glucocorticoid sensitivity was demonstrated in samples collected in the afternoon. Intra-individual variation from samples collected in the morning was 13.0 and 12.7% for the IL-6 and TNF-α responses with the respective inter-individual variations of 9.7 and 7.9%.
Conclusion: The DSCP assay was superior to the reference method and was sufficiently sensitive to detect diurnal variation in control subjects. The biological variation data supported the use of a population-based reference interval. The assay is suitable for screening of glucocorticoid resistance phenotypes and may provide insight into cortisol metabolism in critically ill patients, asthmatics, and patients with inflammatory bowel disease provided that the variation due to delayed processing and time of collection are considered.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article
Collections: ERA 2012 Admin Only
School of Biomedical Sciences Publications
 
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Created: Wed, 19 Oct 2011, 10:09:54 EST by John Cardinal on behalf of School of Biomedical Sciences