title: Increased production of tumor necrosis factor alpha, and not of interferon gamma, preceding disease activity in patients with multiple sclerosis.
abstract: OBJECTIVE
  To study whether tumor necrosis factor (TNF) alpha or interferon (IFN) gamma production by stimulated white blood cells precedes or accompanies clinical and magnetic resonance imaging signs of disease activity in patients with multiple sclerosis.
  
  
  METHODS
  Prospective study with a follow-up of 9 months.
  
  
  METHODS
  Patients visiting an outpatient university clinic.
  
  
  METHODS
  The 30 Amsterdam-based patients (28 completing all evaluations) participating in a multicenter, randomized, placebo-controlled, double-blind trial of a chimeric anti-CD4 antibody in the treatment of active relapsing-remitting and secondary progressive multiple sclerosis. Patients in both treatment arms were included, because for these patients anti-CD4 treatment in this study did not affect TNF-alpha and IFN-gamma production and did not reduce signs of disease activity on magnetic resonance imaging.
  
  
  METHODS
  Distribution of classes of TNF-alpha and IFN-gamma production (expressed as z scores) in patients with or without clinical or magnetic resonance imaging signs of disease activity.
  
  
  RESULTS
  One month preceding exacerbations of multiple sclerosis, there was a shift toward higher z scores of TNF-alpha production (P<.05), but not of IFN-gamma production. There was no statistically significant relationship between IFN-gamma and TNF-alpha production and magnetic resonance imaging markers of multiple sclerosis activity.
  
  
  CONCLUSIONS
  The production of TNF-alpha, and not of IFN-gamma, is significantly higher in patients with multiple sclerosis before exacerbations than in patients with stable disease. Although present, this relationship is too weak to use TNF-alpha production as a surrogate marker of disease activity in multiple sclerosis.
authors.affiliation: Department of Neurology, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: B W
authors.initials: BW
authors.lastname: van Oosten
authors.forename: F
authors.initials: F
authors.lastname: Barkhof
authors.forename: P E
authors.initials: PE
authors.lastname: Scholten
authors.forename: B M
authors.initials: BM
authors.lastname: von Blomberg
authors.forename: H J
authors.initials: HJ
authors.lastname: Adèr
authors.forename: C H
authors.initials: CH
authors.lastname: Polman
mesh_terms: D000328:Adult; D015415:Biomarkers; D018450:Disease Progression; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D008279:Magnetic Resonance Imaging; D008297:Male; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology
chemical_list: D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma