Long-term effect of IFN beta 1b treatment on the spontaneous and induced expression of IL-10 and TGF beta 1 in MS patients

Interferon-beta (IFN beta) is an effective treatment that lessens the frequ ency and severity of exacerbations in relapsing-remitting multiple sclerosi s (RRMS). The mechanism of action of IFN beta 1b may be by upregulating ant iinflammatory cytokines levels. We studied the effect of IFN beta 1b treatm ent on the in vivo gene expression and protein synthesis of two immunosuppr essive cytokines, IL-10 and TGF beta1, and its persistence with chronic the rapy. Peripheral blood samples were obtained from 16 patients before and af ter 3, 6 and 12 months of IFN beta 1b treatment. Eleven patients did not ha ve any clinical relapse, whereas the other five each had one clinical exace rbation during the study. We employed a highly sensitive RT-PCR technique t o study the spontaneous gene expression of IL-10 and TGF beta1. Protein con centration in serum and in culture supernatants from mitogen-stimulated cel ls were measured by ELISA. In the group of patients who remained clinically stable during the study, IL-10 mRNA levels decreased significantly after 6 months of treatment to normalize at 1 year of therapy as compare with the initial values. In the five patients who relapsed, mRNA IL-10 levels were s ignificantly diminished at 3, 6, and 12 months of therapy. IL-10 serum leve ls did not vary significantly in any group of patients during the study. Tr eatment did not modulate mRNA or serum levels of TGF beta1 at any time peri od in the group of stable patients. However, in the five patients who relap sed, TGF beta1 mRNA significantly decreased at 6 and 12 months of therapy. IFN beta 1b treatment was unable to restore the initial low mitogen-induced production of IL-10; only after 1 year of therapy was a slight increase ob served. Cytokine therapy did not affect the mitogen-induced production of T GF beta1. We can conclude that chronic administration of IFN beta 1b does n ot result in an upregulation of IL-10 and TGF beta1. (C) 2000 Elsevier Scie nce B.V. All rights reserved.