Tumor necrosis factor O and its receptors in multiple sclerosis

We characterized the extent and timing of tumor necrosis factor (TNF) α-system activation during multiple sclerosis (MS). We measured serum levels of soluble TNFOC, soluble TNFαreceptor 1 (R1) and soluble TNFα receptor 2 (R2) in 65 MS patients in different phases of disease and we found no differences between MS patients and healthy controls and no correlation with clinical relapses, presence of gadolinium-enhancing brain-magnetic resonance imaging (MRI) lesions and bioactivity of TNFa. We also measured, in 8 additional MS patients peripheral blood mononuclear cells (PBMC) mRNA and serum levels of TNFCX, Rl and R2 every 15 days for 5 menths aerear elinical evcavhation PRMC TNFα R1 and R2 mRNA and serum levels of soluble Rl and R2, but not TNFa, fluctuated concordantly (p<0.05) and peaked a mean of 6 weeks before clinical and MRI evidence of disease activity. Moreover we found a significatively positive correlation between cumulative TNFa and R2 mRNA levels and the number of clinical attacks recorded in the 8 patients studied serially. Our study shows that absolute serum levels of TNFa, R1 and R2 in MS patients do not differ from those of healthy individuals. Although within normal values, the transcription and production rate of all these molecules fluctuate concordantly in the peripheral blood during the course of disease.