Sensitivity to glucocorticoids is decreased in relapsing remitting multiple sclerosis

Lisa M L van Winsen, Daan F R Muris, Chris H Polman, Christine D Dijkstra, Timo K van den Berg, Bernard M J Uitdehaag

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Endogenous glucocorticoids (GC), which are under control of the hypothalamic-pituitary-adrenal axis, play an important role in controlling chronic inflammatory demyelinating diseases, like multiple sclerosis (MS). Increased hypothalamic-pituitary-adrenal axis activity has been found in MS patients and appeared to be negatively associated with acute inflammation. Exogenous GC are frequently used to treat relapses in MS, but the response to this treatment differs among patients, suggesting differences in sensitivity to GC. Previous, relatively small studies investigating GC sensitivity have yielded conflicting results. In the present study, we have investigated GC sensitivity in peripheral blood cells of MS patients (n = 117) and healthy controls (n = 45). GC sensitivity was measured by the in vitro suppressive effect of GC on lipopolysaccharide-stimulated TNF-alpha production. Blood cells of MS patients, especially relapsing remitting MS patients, were less sensitive to GC compared with blood cells of healthy controls. This turned out to be unrelated to previous treatment with exogenous GC expressed as frequency of courses of iv steroids or interval since last course. The use of interferon beta was found to be associated with a lower GC sensitivity. However, after correction for the use of interferon beta, relapsing remitting MS patients remained less sensitive to GC.

Original languageEnglish
Pages (from-to)734-40
Number of pages7
JournalThe Journal of clinical endocrinology and metabolism
Volume90
Issue number2
DOIs
Publication statusPublished - Feb 2005

Cite this

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title = "Sensitivity to glucocorticoids is decreased in relapsing remitting multiple sclerosis",
abstract = "Endogenous glucocorticoids (GC), which are under control of the hypothalamic-pituitary-adrenal axis, play an important role in controlling chronic inflammatory demyelinating diseases, like multiple sclerosis (MS). Increased hypothalamic-pituitary-adrenal axis activity has been found in MS patients and appeared to be negatively associated with acute inflammation. Exogenous GC are frequently used to treat relapses in MS, but the response to this treatment differs among patients, suggesting differences in sensitivity to GC. Previous, relatively small studies investigating GC sensitivity have yielded conflicting results. In the present study, we have investigated GC sensitivity in peripheral blood cells of MS patients (n = 117) and healthy controls (n = 45). GC sensitivity was measured by the in vitro suppressive effect of GC on lipopolysaccharide-stimulated TNF-alpha production. Blood cells of MS patients, especially relapsing remitting MS patients, were less sensitive to GC compared with blood cells of healthy controls. This turned out to be unrelated to previous treatment with exogenous GC expressed as frequency of courses of iv steroids or interval since last course. The use of interferon beta was found to be associated with a lower GC sensitivity. However, after correction for the use of interferon beta, relapsing remitting MS patients remained less sensitive to GC.",
keywords = "Adult, Dexamethasone/pharmacology, Female, Glucocorticoids/pharmacology, Humans, Male, Middle Aged, Multiple Sclerosis/blood, Reference Values, Tumor Necrosis Factor-alpha/metabolism",
author = "{van Winsen}, {Lisa M L} and Muris, {Daan F R} and Polman, {Chris H} and Dijkstra, {Christine D} and {van den Berg}, {Timo K} and Uitdehaag, {Bernard M J}",
year = "2005",
month = "2",
doi = "10.1210/jc.2004-0306",
language = "English",
volume = "90",
pages = "734--40",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
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Sensitivity to glucocorticoids is decreased in relapsing remitting multiple sclerosis. / van Winsen, Lisa M L; Muris, Daan F R; Polman, Chris H; Dijkstra, Christine D; van den Berg, Timo K; Uitdehaag, Bernard M J.

In: The Journal of clinical endocrinology and metabolism, Vol. 90, No. 2, 02.2005, p. 734-40.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Sensitivity to glucocorticoids is decreased in relapsing remitting multiple sclerosis

AU - van Winsen, Lisa M L

AU - Muris, Daan F R

AU - Polman, Chris H

AU - Dijkstra, Christine D

AU - van den Berg, Timo K

AU - Uitdehaag, Bernard M J

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N2 - Endogenous glucocorticoids (GC), which are under control of the hypothalamic-pituitary-adrenal axis, play an important role in controlling chronic inflammatory demyelinating diseases, like multiple sclerosis (MS). Increased hypothalamic-pituitary-adrenal axis activity has been found in MS patients and appeared to be negatively associated with acute inflammation. Exogenous GC are frequently used to treat relapses in MS, but the response to this treatment differs among patients, suggesting differences in sensitivity to GC. Previous, relatively small studies investigating GC sensitivity have yielded conflicting results. In the present study, we have investigated GC sensitivity in peripheral blood cells of MS patients (n = 117) and healthy controls (n = 45). GC sensitivity was measured by the in vitro suppressive effect of GC on lipopolysaccharide-stimulated TNF-alpha production. Blood cells of MS patients, especially relapsing remitting MS patients, were less sensitive to GC compared with blood cells of healthy controls. This turned out to be unrelated to previous treatment with exogenous GC expressed as frequency of courses of iv steroids or interval since last course. The use of interferon beta was found to be associated with a lower GC sensitivity. However, after correction for the use of interferon beta, relapsing remitting MS patients remained less sensitive to GC.

AB - Endogenous glucocorticoids (GC), which are under control of the hypothalamic-pituitary-adrenal axis, play an important role in controlling chronic inflammatory demyelinating diseases, like multiple sclerosis (MS). Increased hypothalamic-pituitary-adrenal axis activity has been found in MS patients and appeared to be negatively associated with acute inflammation. Exogenous GC are frequently used to treat relapses in MS, but the response to this treatment differs among patients, suggesting differences in sensitivity to GC. Previous, relatively small studies investigating GC sensitivity have yielded conflicting results. In the present study, we have investigated GC sensitivity in peripheral blood cells of MS patients (n = 117) and healthy controls (n = 45). GC sensitivity was measured by the in vitro suppressive effect of GC on lipopolysaccharide-stimulated TNF-alpha production. Blood cells of MS patients, especially relapsing remitting MS patients, were less sensitive to GC compared with blood cells of healthy controls. This turned out to be unrelated to previous treatment with exogenous GC expressed as frequency of courses of iv steroids or interval since last course. The use of interferon beta was found to be associated with a lower GC sensitivity. However, after correction for the use of interferon beta, relapsing remitting MS patients remained less sensitive to GC.

KW - Adult

KW - Dexamethasone/pharmacology

KW - Female

KW - Glucocorticoids/pharmacology

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KW - Male

KW - Middle Aged

KW - Multiple Sclerosis/blood

KW - Reference Values

KW - Tumor Necrosis Factor-alpha/metabolism

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