title: Reduction of both pro- and anti-inflammatory cytokines after 6 months of interferon beta-1a treatment of multiple sclerosis.
abstract: Treatment of multiple sclerosis (MS) with interferon beta (IFNbeta) reduces relapse rate, magnetic resonance imaging (MRI) activity and progression of disability. It has been suggested that this beneficial effect is paralleled by an inhibition of proinflammatory cytokines such as interferon gamma (IFNgamma) and tumor necrosis factor alpha (TNFalpha) and an induction of anti-inflammatory cytokines such as interleukin-4 (IL-4) and interleukin-10 (IL-10). In this study, we record a reduced number of spontaneously IFNgamma mRNA-expressing cerebrospinal fluid mononuclear cells (CSF-MC) and IFNgamma, TNFalpha and IL-10 mRNA-expressing peripheral blood mononuclear cells (PBMC) after 6 months of IFNbeta-1a treatment, paralleled by a decreased purified protein derivate (PPD)-stimulated and unstimulated IFNgamma secretion by PBMC. These effects were not apparent after 2 weeks of treatment, and IFNbeta-1a induced IFNgamma production by naive PBMC in vitro. We did not record increased numbers of IL-4 mRNA-expressing CSF-MC or PBMC, increased plasma IL-10 levels, increased numbers of IgG, A or M secreting plasma cells or in vitro induction of IL-10 production by IFNbeta-1a. We conclude that long-term cytokine modulation by IFNbeta-1a differs from acute effects and that downregulation of both pro- and anti-inflammatory cytokines, rather than a shift in the cytokine profile, is apparent after 6 months of IFNbeta-1a treatment of MS patients.
authors.affiliation: Department of Medicine, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden. mohsen.khademi@cmm.ki.se
authors.forename: M
authors.initials: M
authors.lastname: Khademi
authors.forename: E
authors.initials: E
authors.lastname: Wallström
authors.forename: M
authors.initials: M
authors.lastname: Andersson
authors.forename: F
authors.initials: F
authors.lastname: Piehl
authors.forename: R
authors.initials: R
authors.lastname: Di Marco
authors.forename: T
authors.initials: T
authors.lastname: Olsson
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D002452:Cell Count / Q000187:drug effects; D002478:Cells, Cultured; D002555:Cerebrospinal Fluid / Q000166:cytology / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D014373:Tuberculin / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D012333:RNA, Messenger; D014373:Tuberculin; D016899:Interferon-beta; D007371:Interferon-gamma; D000068556:Interferon beta-1a