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 necrosis factor (TNF)-alpha mRNA by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in unstimulated peripheral blood mononuclear cells (MNCs) of 15 relapsing-remitting multiple sclerosis (MS) patients who underwent 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 expanded disability status score (EDSS). At the same time the expression of TNF-alpha mRNA was assessed in 10 healthy age-matched control subjects. All MS 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 untreated patients and in 13 out of the 15 patients who underwent IFN-beta 1a treatment. The higher TNF-alpha mRNA was evident in patients with gadolinium-enhancing lesions. At the 6-month follow-up, 13 out of the 15 untreated patients still had detectable values of TNF-alpha mRNA and no significant difference emerged when compared with basal time. On the contrary, the expression of TNF-alpha mRNA was absent at the same time in nine out of the 15 patients treated with IFN-beta 1a. A longitudinal analysis carried out monthly in 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 immunoenhancing effect of IFN-beta 1a. This early activation is followed by an inhibitory effect of IFN-beta 1a on TNF-alpha mRNA expression in about 2/3 of treated MS patients when assessed at 6 months. Further long-term studies are needed 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.
Sarchielli
P
P
Department of Neuroscience, Neurological Clinic, University of Perugia, Italy. neuro@netemedia.net
Critelli
A
A
Greco
L
L
Sokola
E
E
Floridi
A
A
Gallai
V
V
D000328:Adult; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta; D000068556:Interferon beta-1a