Increased Production of Tumor Necrosis Factor α, and Not of Interferon γ, Preceding Disease Activity in Patients With Multiple Sclerosis

• Published in: Archives of neurology (Chicago) Vol. 55; no. 6; pp. 793 - 798
• Main Authors: van Oosten, Bob W, Barkhof, Frederik, Scholten, Petra E. T, von Blomberg, B. Mary E, Adèr, Herman J, Polman, Chris H
• Format: Journal Article
• Language: English
• Published: Chicago, IL American Medical Association 01.06.1998
• Subjects: Adult; Biological and medical sciences; Biomarkers; Disease Progression; Female; Humans; Interferon-gamma - biosynthesis; Interferon-gamma - immunology; Magnetic Resonance Imaging; Male; Medical sciences; Multiple Sclerosis - diagnosis; Multiple Sclerosis - immunology; Multiple Sclerosis - pathology; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; Prospective Studies; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - immunology; Human; Nervous system diseases; Multiple sclerosis; Disease; Cytokine; Exploration; Nuclear magnetic resonance imaging; Inflammatory disease; Symptomatology; Central nervous system disease; Medical imagery; Evolution; Tumor necrosis factor α; Gamma interferon
• ISSN: 0003-9942; 1538-3687
• DOI: 10.1001/archneur.55.6.793

OBJECTIVE To study whether tumor necrosis factor (TNF) α or interferon (IFN) γ 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-α and IFN-γ production and did not reduce signs of disease activity on magnetic resonance imaging. MAIN OUTCOME MEASURE Distribution of classes of TNF-α and IFN-γ 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-α production (P<.05), but not of IFN-γ production. There was no statistically significant relationship between IFN-γ and TNF-α production and magnetic resonance imaging markers of multiple sclerosis activity. CONCLUSION The production of TNF-α, and not of IFN-γ, 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-α production as a surrogate marker of disease activity in multiple sclerosis.Arch Neurol. 1998;55:793-798-->