Suppressive effect of glucocorticoids on TNF-alpha production is associated with their clinical effect in multiple sclerosis.
A reduced sensitivity to glucocorticoids can affect the clinical effect of treatment with high-dose intravenous methylprednisolone in multiple sclerosis. We prospectively studied 27 multiple sclerosis patients who were treated with intravenous methylprednisolone. Before and after treatment in vitro stimulated TNF-alpha production in blood cells and the effect of in vitro administered glucocorticoids were determined as a measure of glucocorticoid sensitivity. The suppression of TNF-alpha production after intravenous methylprednisolone, and the in vitro suppressive effect of glucocorticoids prior to treatment was related to subsequent clinical improvement after intravenous methylprednisolone. The results suggest the existence of a partial glucocorticoid resistance, in a subgroup of multiple sclerosis patients, which may have implications for treatment efficacy.
van Winsen
Lisa M L
LM
Department of Neurology, MS Centre Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.
Polman
Chris H
CH
Dijkstra
Christine D
CD
Tilders
Fred J H
FJ
Uitdehaag
Bernard M J
BM
D000328:Adult; D015415:Biomarkers / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology; D004185:Disability Evaluation; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004351:Drug Resistance; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D011446:Prospective Studies; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
D015415:Biomarkers; D005938:Glucocorticoids; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D008775:Methylprednisolone