Tumor Necrosis Factor-alpha Precedes
Multiple Sclerosis Activity

Bob W. van Oosten, MD; Frederik Barkhof, MD; Petra E. T. Scholten; B. Mary E. von Blomberg, PhD; Herman J. Adlèr, PhD; Chris H. Polman, MD
Arch Neurol June 1998;55:793-798
Free Univ Hospital, Dept of Neurology, Amsterdam, The Netherlands
UI # 98288459

To study whether Tumor Necrosis Factor alpha (TNF-alpha) or Interferon-gamma (IFN-gamma) production precedes or accompanies clinical and Magnetic Resonance Imaging signs of disease activity in patients with Multiple Sclerosis, by stimulated White Blood Cells (Leukocytes).

Design & Setting
Prospective study with a follow-up of 9 months, in patients visiting an outpatient Univclinic.

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.

Main Outcome Measure
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.

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.

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.

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