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

作者：Teixeira Bruna; Bittencourt Vera Carolina B; Ferreira Thais B; Kasahara Taissa M; Barros Priscila O; Alvarenga Regina; Hygino Joana; Andrade Regis M; Andrade Arnaldo F; Bento Cleonice A M^*

来源：Clinical Immunology, 2013, 148(2): 209-218.

DOI：10.1016/j.clim.2013.05.012

• Multiple sclerosis
• Lipopolysaccharide
• Cytokines
• Th17
• IL-10
• 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.

• 出版日期2013-8