Interferon beta-1b treatment modulates TNFα and IFNγ spontaneous gene expression in MS

Background: Interferon beta (IFN beta) lessens the overall frequency of acute attacks in patients with the relapsing-remitting form of multiple sclerosis (RRMS). IFN beta may act by decreasing the synthesis of inflammatory cytokines. Objectives: To determine whether IFN beta-1b treatment had an initial and sustained effect on the in vivo synthesis and secretion of tumor necrosis factor or (TNF alpha) and IFN gamma: Methods: A highly sensitive reverse-transcriptase PGR technique was used to measure baseline levels of mRNA in freshly isolated cells from patients before therapy and at 3, 6, and 12 months of treatment. Also, protein concentration was measured in serum and in culture supernatants from mitogen-stimulated cells. The authors studied 16 patients, of whom 11 did not, have clinical exacerbations, whereas 5 had one clinical relapse: each during;the study. Results: Mean values of TNF alpha mRNA levels in the 11 stable patients decreased significantly at 3 and 6 months of treatment in comparison with initial data. After 6 months of therapy, IFN beta-1b downmodulated TNF alpha transcripts in the 5 patients who experienced relapse. In this group of patients, TNF alpha levels rose sharply to reach pretreated values at 1 year of IFN beta-1b treatment. At the beginning of therapy, 6 patients had high concentrations of serum TNF alpha which decreased to normal values following IFN beta-1b therapy. IFN gamma mRNA expression also diminished after 6 and 12 months of IFN beta-1b therapy in the group of stable patients, whereas nonrelevant variations were observed in patients who had one relapse. Initially, patients' peripheral mononuclear cells: secreted diminished;amounts of TNF alpha and IFN gamma on PHA + PMA mitogen stimulation in comparison with normal control subjects. After 1 year of therapy, IFN beta-1b restored the normal production of TNF alpha, whereas therapy did not restore IFN gamma secretion to control values. Conclusion: IFN beta-1b decreases the spontaneous expression of two proinflammatory cytokines.