Low sensitivity to glucocorticoid inhibition of in vitro Th17-related cytokine production in multiple sclerosis patients is related to elevated plasma lipopolysaccharide levels

Clin Immunol. 2013 Aug;148(2):209-18. doi: 10.1016/j.clim.2013.05.012. Epub 2013 May 28.


Exogenous glucocorticoid plays an important role in controlling clinical relapses of multiple sclerosis (MS), but the response to this treatment differs among patients. In this study, T-cell proliferation and IL-17 production were less sensitive to hydrocortisone (HC) inhibition in MS patients than healthy individuals, mainly in CD8(+) compartment. Furthermore, in vitro IL-17 production was positively related with neurological disability and its release was proportional to IL-23 and IL-6 productions by LPS-activated monocytes. Interestingly, elevated LPS levels were quantified in the plasma of MS patients, and their levels were directly related to in vivo IL-6 production. Finally, HC-resistance in reducing IL-17 production by polyclonally-activated CD8(+) T cells was particularly observed among MS patients with higher in vivo LPS levels. In summary, the results indicate that T-cells derived from MS patients show an enhanced Th17-like phenotype that is directly associated with neurological disability, resistance to glucocorticoid inhibition and elevated bacterial translocation.

Keywords: CD8(+) T cells; Cytokines;; IL-10;; Lipopolysaccharide;; Multiple sclerosis;; Th17;.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cytokines / antagonists & inhibitors
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Female
  • Gene Expression Regulation / drug effects
  • Glucocorticoids / pharmacology*
  • Humans
  • Hydrocortisone / pharmacology
  • Lipopolysaccharides / blood*
  • Lipopolysaccharides / metabolism
  • Male
  • Middle Aged
  • Monocytes / drug effects
  • Monocytes / immunology
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / metabolism
  • Th17 Cells / drug effects
  • Th17 Cells / physiology*
  • Young Adult


  • Cytokines
  • Glucocorticoids
  • Lipopolysaccharides
  • Hydrocortisone