Tumor necrosis factor(TNF)-αconverting enzyme(TACE,also called ADAM17)is a key sheddase that releases TNF-αfrom its inactive cell-bound precursor.TACE protein expression levels in peripheral blood mononuclear cells were measured by Western blot analysis in 20 healthy controls and 80 multiple sclerosis(MS)patients before and after treatment with IFNβ[20 patients with primary progressive(PP)MS,20 patients with secondary progressive(SP)MS,and 40 patients with relapsing-remitting(RR)MS(20 patients during clinical remission and 20 patients in relapse)].TNF-αserum levels were also measured by enzyme-linked immunoassay in the MS patients and healthy controls.TACE protein expression levels were lower in healthy controls and PPMS patients compared with SPMS patients and RRMS patient during clinical remission.No differences in TACE protein levels were observed between RRMS patients in relapse and during remission.TACE protein levels were increased in PPMS patients treated with IFNβ.Serum TNFαlevels were higher in RRMS patients in relapse compared with RRMS patients during remission,and positive and negative correlations were found between TACE protein expression and serum TNF-αlevels in RRMS patients during relapse and during remission respectively.These findings point to different regulatory mechanisms of the TACE-TNF-αpathway in the clinical MS subtypes and expand the role of TACE in MS pathogenesis. Tumor necrosis factor (TNF) -αconverting enzyme (TACE, also ADAM17) is a key sheddase that releases TNF-αfrom its inactive cell-bound precursor. TACE protein expression levels in peripheral blood mononuclear cells were measured by Western blot analysis in 20 healthy controls and 80 multiple sclerosis (MS) patients before and after treatment with IFNβ [20 patients with primary progressive (PP) MS, 20 patients with secondary progressive (SP) MS, and 40 patients with relapsing-remitting during clinical remission and 20 patients in relapse)]. TNF-α serum levels were also measured by enzyme-linked immunoassay in the MS patients and healthy controls. TACE protein expression levels were lower in healthy controls and PPMS patients compared with SPMS patients and RRMS patient during clinical remission. No differences in TACE protein levels were observed between RRMS patients in relapse and during remission. TACE protein levels were increased in PPMS patients treated with IFNβ. Fαlevels were more in RRMS patients in relapse, and positive and negative correlations were found between TACE protein expression and serum TNF-αlevels in RRMS patients during relapse and during repective respectively. These findings point to different regulatory mechanisms of the TACE-TNF-αpathway in the clinical MS subtypes and expand the role of TACE in MS pathogenesis.