TUMOR-NECROSIS-FACTOR PRODUCTION CAPACITY AS A POTENTIALLY USEFUL PARAMETER TO MONITOR DISEASE-ACTIVITY IN MULTIPLE-SCLEROSIS

The aim of this study was to develop a test allowing to monitor diseas e activity in patients with multiple sclerosis (MS), A simple, fast an d reliable test was used to assess the cytokine production capacity of blood leucocytes, The whole blood test (WET) involved iii vitro stimu lation of a whole blood sample with either the mitogen phytohaemagglut inin (PHA), or specific antigens, We focused our attention on the prod uction of tumor necrosis factor alpha (TNF), because of the possible i nvolvement of this cytokine in MS pathogenesis. Under in vitro stimula tion with PHA or MBP, TNF production was found to be significantly hig her in patients during the clinical relapses than during remissions, T he increment of TNF production correlated with the severity of the rel apses,as determined by the,modification of Kurtzke EDSS scale, Moreove r,each clinical relapse appeared to be preceded by a peak of TNF produ ction, We then retrospectively analysed 21 patients with the relapsing -remitting form of the disease, in whom the WET was performed: every 2 -4 weeks, for periods ranging from 16 to 52 months, Seventy-three peak s of TNF production (defined as the doubling or more of the individual baseline value, which was found to be stable for each patient during remissions), and 47 relapses, including 36 objective and 11 subjective , were observed, Forty-seven out of the 73 TNF peaks were followed by or concomitant with a clinical relapse, In 10 out of the 26 cases wher e no relapse followed the TNF peak, another cause (mainly infections) of increased TNF production was found, Thus, by excluding other causes , the specificity of the WET, Le., the probability to develop a relaps e when a TNF peak was found to be 74.6% (47/63), The sensitivity of th e WBT was 100%, since all the 47 relapses were preceded by a TNF peak, Assessment of TNF production capacity by the WET may thus be useful i n the follow-up of MS patients, particularly for the follow-up of vari ous treatments, Information provided by the WET may also be useful to orientate the therapeutic decision for an incipient relapse, Earlier t reatment is likely to result in an improved prevention of neurological damage.