Expression of TNF-alpha mRNA by peripheral blood mononuclear cells of multiple sclerosis patients treated with IFN-beta 1A

The aim of the present study was to verify the expression of tumour necrosi s factor (TNF)-alpha mRNA by semiquantitative reverse transcriptase-polymer ase chain reaction (RT-PCR) in unstimulated peripheral blood mononuclear ce lls (MNCs) of 15 relapsing-remitting multiple sclerosis (MS) patients who u nderwent treatment with IFN-beta 1a (6 millions of international units (MIU ) i.m. once a week) and in 15 untreated MS patients matched for age and exp anded disability status score (EDSS). At the same time the expression of TN F-alpha mRNA was assessed in 10 healthy age-matched control subjects. All M S patients were assessed at the basal time and after 6 months. At the basal time, the band of TNF-alpha mRNA was detectable in 12 out of the 15 untrea ted patients and in 13 out of the 15 patients who underwent IFN-beta 1a tre atment. The higher TNF-alpha mRNA was evident in patients with gadolinium-e nhancing lesions. At the 6-month follow-up, 13 out of the 15 untreated pati ents still had detectable values of TNF-alpha mRNA and no significant diffe rence emerged when compared with basal time. On the contrary, the expressio n of TNF-alpha mRNA was absent at the same time in nine out of the 15 patie nts treated with IFN-beta 1a, A longitudinal analysis carried out monthly i n eight MS patients (four untreated and four treated) revealed a transient increase in TNF-alpha mRNA expression in MNCs of all four treated patients in the first 3 months, supporting previous findings of an early immunoenhan cing effect of IFN-beta la, This early activation is followed by an inhibit ory effect of IFN-beta 1a on TNF-alpha mRNA expression in about 2/3 of trea ted MS patients when assessed at 6 months. Further long-term studies are ne eded to confirm this immunomodulatory effect of IFN-beta 1a not only on TNF -alpha but also on other cytokines of Th-1 and Th-2 types. (C) 2001 Academi c Press.