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Increased Production of Tumor Necrosis Factor  , and Not of Interferon  , Preceding Disease Activity in Patients With Multiple Sclerosis
Bob W. van Oosten, MD;
Frederik Barkhof, MD;
Petra E. T. Scholten;
B. Mary E. von Blomberg, PhD;
Herman J. Adèr, PhD;
Chris H. Polman, MD
Arch Neurol. 1998;55:793-798.
Objective To study whether tumor necrosis factor (TNF)  or interferon (IFN)  production by stimulated white blood cells precedes or accompanies clinical and magnetic resonance imaging signs of disease activity in patients with multiple sclerosis.
Design Prospective study with a follow-up of 9 months.
Setting Patients visiting an outpatient university clinic.
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.
From the Departments of Neurology (Drs van Oosten and Polman) and Pathology (Ms Scholten and Dr von Blomberg), and the MS-MRI Centre (Dr Barkhof), Free University Hospital, and Department of Epidemiology and Biostatistics, Faculty of Medicine, Free University (Dr Adèr), Amsterdam, the Netherlands.
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