title: The effects of interferon-alpha2a on concentrations of immunoglobulins, complement and lymphocytes in patients with multiple sclerosis.
abstract: Multiple sclerosis (MS) patients treated with type I interferon experience reduced disease activity. Because immunoglobulins (Igs), complement and lymphocytes have been given a role in the pathogenesis of MS, we investigated the longitudinal effect of interferon-alpha2a (IFNA) on the variability of these parameters. Patients were treated for 6 months with 4.5 million international units (MIU) IFNA (24 patients), 9.0 MIU IFNA (21 patients) or placebo (23 patients). IFNA induced a significant increase in concentrations of total IgG and IgG subclasses 1, 3 and 4. At 6 months, the mean concentration of IgG had increased by 1.51 g/l (CI: 0.82, 2.21) in the 9.0 MIU IFNA group. There was no significant effect of IFNA treatment on concentrations of IgG2 and IgA, while the effect on IgM was borderline significant. After 6 months, IgM had increased by 0.29 g/l (CI: -0.01, 0.65) in the 9.0 MIU IFNA group. IFNA induced a significant increase in the concentration of C1 inhibitor (INH). At 3 months, the mean concentration of C1 INH had increased by 0.033 g/l (CI: 0.01, 0.05). At 3 months, C4 had increased by 0.05 g/l (CI: 0.01, 0.09) in the 9.0 MIU IFNA group. The effect of IFNA on C4 was inconclusive but indicates an effect during the initial phase of the treatment. C3 showed no significant treatment-mediated change. IFNA induced a significant decrease in lymphocyte concentrations by 0.56 x 106 lymphocytes/ml (CI: -0.81, -0.31) at 3 months. There were no significant associations between changes in immune parameters and changes in clinical and magnetic resonance imaging scores. The results verify that IFNA modulates and activates both the innate and the adaptive arms of the immune system. The observations should be of relevance when evaluating mechanisms of action of IFN treatment in MS.
authors.affiliation: Department of Microbiology and Immunology, The Gade Institute, Bergen, Norway. ulvestad@haukeland.no
authors.forename: E
authors.initials: E
authors.lastname: Ulvestad
authors.forename: J H
authors.initials: JH
authors.lastname: Aarseth
authors.forename: C
authors.initials: C
authors.lastname: Vedeler
authors.forename: H
authors.initials: H
authors.lastname: Nyland
authors.forename: K-M
authors.initials: KM
authors.lastname: Myhr
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003165:Complement System Proteins / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D007136:Immunoglobulins / Q000097:blood / Q000187:drug effects*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008214:Lymphocytes / Q000187:drug effects*; D008279:Magnetic Resonance Imaging; D009103:Multiple Sclerosis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D011994:Recombinant Proteins
chemical_list: D000970:Antineoplastic Agents; D007136:Immunoglobulins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D003165:Complement System Proteins