title: Low sensitivity to glucocorticoid inhibition of in vitro Th17-related cytokine production in multiple sclerosis patients is related to elevated plasma lipopolysaccharide levels.
abstract: 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.
authors.affiliation: Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Brazil.
authors.forename: Bruna
authors.initials: B
authors.lastname: Teixeira
authors.forename: Vera Carolina B
authors.initials: VC
authors.lastname: Bittencourt
authors.forename: Thais B
authors.initials: TB
authors.lastname: Ferreira
authors.forename: Taissa M
authors.initials: TM
authors.lastname: Kasahara
authors.forename: Priscila O
authors.initials: PO
authors.lastname: Barros
authors.forename: Regina
authors.initials: R
authors.lastname: Alvarenga
authors.forename: Joana
authors.initials: J
authors.lastname: Hygino
authors.forename: Regis M
authors.initials: RM
authors.lastname: Andrade
authors.forename: Arnaldo F
authors.initials: AF
authors.lastname: Andrade
authors.forename: Cleonice A M
authors.initials: CA
authors.lastname: Bento
mesh_terms: D000328:Adult; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000097:blood* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects / Q000502:physiology*; D055815:Young Adult
chemical_list: D016207:Cytokines; D005938:Glucocorticoids; D008070:Lipopolysaccharides; D006854:Hydrocortisone
keywords: CD8(+) T cells; Cytokines;; IL-10;; Lipopolysaccharide;; Multiple sclerosis;; Th17;