Corticosteroid resistance in a subpopulation of multiple sclerosis patients as measured by ex vivo dexamethasone inhibition of LPS induced IL-6 production.
We assessed corticosteroid sensitivity in multiple sclerosis (MS) patients compared to control subjects, using an in vitro assay of dexamethasone (Dex) inhibition of lipopolysaccharide (LPS) stimulated-blood interleukin-6 production. Significantly higher concentrations of dexamethasone were needed to obtain 50%-inhibition (ID(50)) of in vitro LPS stimulated interleukin (IL)-6 production (28.4 x 10(-7) M) in relapsing-remitting MS (RRMS) patients compared to chronic progressive MS (CPMS) patients (6.2 x 10(-7) M) or compared to controls (3.0 x 10(-7) M). We also found a trend towards worsening of clinical status over time with increasing corticosteroid resistance. These data suggest that corticosteroid sensitivity may be a factor in the pathogenesis and could be used for prognosis of MS.
DeRijk
Roel H
RH
Section in Neuroendocrine Immunology and Behavior, National Institute of Mental Health, National Institutes of Health, 36 Convent Drive (MSC 4020), Bethesda, MD 20892-4020, USA. rderijk@rijngeestgroep.nl
Eskandari
Farideh
F
Sternberg
Esther M
EM
D000305:Adrenal Cortex Hormones; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001773:Blood Cells / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004351:Drug Resistance / Q000276:immunology*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology*; D020528:Multiple Sclerosis, Chronic Progressive / Q000097:blood / Q000276:immunology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000276:immunology; D011379:Prognosis
D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D003907:Dexamethasone