Interferon beta-1b treatment modulates TNF alpha and IFN gamma spontaneousgene expression in MS

Background: Interferon beta (IFN beta) lessens the overall frequency of acu te attacks in patients with the relapsing-remitting form of multiple sclero sis (RRMS). IFN beta may act by decreasing the synthesis of inflammatory cy tokines. Objectives: To determine whether IFN beta-1b treatment had an init ial and sustained effect on the in vivo synthesis and secretion of tumor ne crosis factor or (TNF alpha) and IFN gamma: Methods: A highly sensitive rev erse-transcriptase PGR technique was used to measure baseline levels of mRN A in freshly isolated cells from patients before therapy and at 3, 6, and 1 2 months of treatment. Also, protein concentration was measured in serum an d in culture supernatants from mitogen-stimulated cells. The authors studie d 16 patients, of whom 11 did not, have clinical exacerbations, whereas 5 h ad one clinical relapse: each during;the study. Results: Mean values of TNF alpha mRNA levels in the 11 stable patients decreased significantly at 3 a nd 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 t he beginning of therapy, 6 patients had high concentrations of serum TNF al pha which decreased to normal values following IFN beta-1b therapy. IFN gam ma mRNA expression also diminished after 6 and 12 months of IFN beta-1b the rapy in the group of stable patients, whereas nonrelevant variations were o bserved in patients who had one relapse. Initially, patients' peripheral mo nonuclear cells: secreted diminished;amounts of TNF alpha and IFN gamma on PHA + PMA mitogen stimulation in comparison with normal control subjects. A fter 1 year of therapy, IFN beta-1b restored the normal production of TNF a lpha, whereas therapy did not restore IFN gamma secretion to control values . Conclusion: IFN beta-1b decreases the spontaneous expression of two proin flammatory cytokines.