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Sensitivity to glucocorticoids is decreased in relapsing remitting multiple sclerosis
Lisa M L van Winsen1, Daan F R Muris, Chris H Polman
1Vrije Universiteit Medical Center, Department of Neurology, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. l.vanwinsen2@vumc.nl
The Journal of Clinical Endocrinology and Metabolism
|November 18, 2004
Summary
Multiple sclerosis patients show reduced sensitivity to glucocorticoids (GC), impacting treatment effectiveness. This reduced sensitivity in immune cells is linked to disease activity and interferon beta use.
Area of Science:
- Neuroimmunology
- Endocrinology
- Pharmacology
Background:
- Glucocorticoids (GC) are crucial for managing chronic inflammatory demyelinating diseases like multiple sclerosis (MS).
- MS patients exhibit altered hypothalamic-pituitary-adrenal axis activity, negatively correlating with inflammation.
- Individual responses to exogenous GC treatment for MS relapses vary, indicating differing GC sensitivity.
Purpose of the Study:
- To investigate glucocorticoid (GC) sensitivity in peripheral blood cells of multiple sclerosis (MS) patients compared to healthy controls.
- To explore factors influencing GC sensitivity in MS, including disease subtype and medication use.
Main Methods:
- Assessed GC sensitivity by measuring the in vitro suppressive effect of GC on lipopolysaccharide-stimulated TNF-alpha production.
- Analyzed peripheral blood cells from 117 MS patients and 45 healthy controls.
- Correlated GC sensitivity with clinical data, including MS subtype, previous GC treatment, and interferon beta use.
Main Results:
- Blood cells from MS patients, particularly those with relapsing-remitting MS, demonstrated lower GC sensitivity than controls.
- This reduced sensitivity was independent of prior exogenous GC treatment frequency or recency.
- Interferon beta use was associated with decreased GC sensitivity, but relapsing-remitting MS patients remained less sensitive even after adjustment.
Conclusions:
- Relapsing-remitting MS patients exhibit intrinsic reduced glucocorticoid sensitivity in peripheral blood cells.
- This finding suggests potential therapeutic implications for GC treatment strategies in MS.
- Further research is warranted to elucidate the mechanisms underlying altered GC sensitivity in MS.