title: Long-term effect of IFNbeta1b treatment on the spontaneous and induced expression of IL-10 and TGFbeta1 in MS patients.
abstract: Interferon-beta (IFNbeta) is an effective treatment that lessens the frequency and severity of exacerbations in relapsing-remitting multiple sclerosis (RRMS). The mechanism of action of IFNbeta1b may be by upregulating antiinflammatory cytokines levels. We studied the effect of IFNbeta1b treatment on the in vivo gene expression and protein synthesis of two immunosuppressive cytokines, IL-10 and TGFbeta1, and its persistence with chronic therapy. Peripheral blood samples were obtained from 16 patients before and after 3, 6 and 12 months of IFNbeta1b treatment. Eleven patients did not have any clinical relapse, whereas the other five each had one clinical exacerbation during the study. We employed a highly sensitive RT-PCR technique to study the spontaneous gene expression of IL-10 and TGFbeta1. Protein concentration in serum and in culture supernatants from mitogen-stimulated cells 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 significantly diminished at 3, 6, and 12 months of therapy. IL-10 serum levels did not vary significantly in any group of patients during the study. Treatment did not modulate mRNA or serum levels of TGFbeta1 at any time period in the group of stable patients. However, in the five patients who relapsed, TGFbeta1 mRNA significantly decreased at 6 and 12 months of therapy. IFNbeta1b treatment was unable to restore the initial low mitogen-induced production of IL-10; only after 1 year of therapy was a slight increase observed. Cytokine therapy did not affect the mitogen-induced production of TGFbeta1. We can conclude that chronic administration of IFNbeta1b does not result in an upregulation of IL-10 and TGFbeta1.
authors.affiliation: Department of Immunology, Hospital Central de Asturias, Universidad de Oviedo, Julián Clavería s/n, 33006, Oviedo, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Gayo
authors.forename: L
authors.initials: L
authors.lastname: Mozo
authors.forename: A
authors.initials: A
authors.lastname: Suárez
authors.forename: A
authors.initials: A
authors.lastname: Tuñon
authors.forename: C
authors.initials: C
authors.lastname: Lahoz
authors.forename: C
authors.initials: C
authors.lastname: Gutiérrez
mesh_terms: D018450:Disease Progression; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D055502:Secondary Prevention; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D016899:Interferon-beta