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

- IL-17-producing T-cells were related to the neurological disability in MS patients.
- Th17-related cytokine production was less susceptible to GC in MS patients.
- High IL-23/IL-6 production by LPS-activated monocytes was observed in MS patients.
- Elevated LPS levels were quantified in the plasma of MS patients.
- In vivo LPS levels were related to GC-resistance of IL-17 production by CD8+ T cells.

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.