INCREASED PRODUCTION OF TUMOR-NECROSIS-FACTOR-ALPHA, AND NOT OF INTERFERON-GAMMA, PRECEDING DISEASE-ACTIVITY IN PATIENTS WITH MULTIPLE-SCLEROSIS

Objective: To study whether tumor necrosis factor (TNF) alpha or inter feron (IFN) gamma production by stimulated white blood cells precedes or accompanies clinical and magnetic resonance imaging signs of diseas e activity in patients with multiple sclerosis. Design: Prospective st udy with a follow-up of 9 months. Setting: Patients visiting an outpat ient 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 antibo dy in the treatment of active relapsing-remitting and secondary progre ssive multiple sclerosis. Patients in both treatment arms were include d, 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 (expres sed as z scores) in patients with or without clinical or magnetic reso nance 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 did not of INF-gamma prod uction. There was no statistically significant relationship between IF N-gamma and TNF-alpha production and magnetic resonance imaging marker s of multiple sclerosis activity. Conclusion: The production of TNF-al pha, and not of IFN-gamma, is significantly higher in patients with mu ltiple sclerosis before exacerbations than in patients with stable dis ease. Although present, this relationship is too weak to use TNF-alpha production as a surrogate marker of disease activity in multiple scle rosis.