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 Abstract Objective To study whether Tumor Necrosis Factor alpha (TNF-) or Interferon-gamma (IFN-) 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. Patients 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- and IFN- production and did not reduce signs of disease activity on Magnetic Resonance Imaging. Main Outcome Measure Distribution of classes of TNF- and IFN- 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- production (P<.05), but not of IFN- production. There was no statistically significant relationship between IFN- and TNF- production and Magnetic Resonance Imaging markers of Multiple Sclerosis activity. Conclusion The production of TNF-, and not of IFN-, 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- production as a surrogate marker of disease activity in Multiple Sclerosis.