Reduced cortisol levels in cerebrospinal fluid and differential distribution of 11β-hydroxysteroid dehydrogenases in multiple sclerosis: Implications for lesion pathogenesis

Claudia Heidbrink, Sebastian F.M. Häusler, Mathias Buttmann, Monika Ossadnik, Herwig M. Strik, Andreas Keller, Dorothea Buck, Evert Verbraak, Marjan van Meurs, Mathias Krockenberger, Matthias Mehling, Michel Mittelbronn, Jon D. Laman, Heinz Wiendl, Jörg Wischhusen*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

21 Citations (Scopus)

Abstract

Relapses during multiple sclerosis (MS) are treated by administration of exogenous corticosteroids. However, little is known about the bioavailability of endogenous steroids in the central nervous system (CNS) of MS patients. We thus determined cortisol and dehydroepiandrosterone (DHEA) levels in serum and cerebrospinal fluid (CSF) samples from 34 MS patients, 28 patients with non-inflammatory neurological diseases (NIND) and 16 patients with other inflammatory neurological diseases (OIND). This revealed that MS patients - in sharp contrast to patients with OIND - show normal cortisol concentrations in serum and lowered cortisol levels in the CSF during acute relapses. This local cortisol deficit may relate to poor local activation of cortisone via 11β-hydroxysteroid dehydrogenase type 1 (11bHSD1) or to inactivation via 11bHSD2. Accordingly, 11bHSD2 was found to be expressed within active plaques, whereas 11bHSD1 was predominantly detected in surrounding " foamy" macrophages. Our study thus provides new insights into the impaired endogenous CNS cortisol regulation in MS patients and its possible relation to MS lesion pathogenesis. Moreover, an observed upregulation of 11bHSD1 in myelin-loaded macrophages in vitro suggests an intriguing hypothesis for the self-limiting nature of MS lesion development. Finally, our findings provide an attractive explanation for the effectivity of high- vs. low-dose exogenous corticosteroids in the therapy of acute relapses.

Original languageEnglish
Pages (from-to)975-984
Number of pages10
JournalBrain, Behavior, and Immunity
Volume24
Issue number6
DOIs
Publication statusPublished - Aug 2010
Externally publishedYes

Keywords

  • 11β-Hydroxysteroid dehydrogenase 1/2
  • Cerebrospinal fluid
  • Cortisol
  • Glucocorticoids
  • Macrophages
  • Multiple sclerosis

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