title: Interferon-beta 1b treatment decreases tumor necrosis factor-alpha and increases interleukin-6 production in multiple sclerosis.
abstract: MS is presumed to be a T-cell-mediated chronic inflammatory disease of the CNS. We examined proliferation and cytokine secretion of mononuclear cells after stimulation with OKT3 [anti-CD3] monoclonal antibody (MAb) or concanavalin A (Con A) in subjects with stable relapsing-remitting MS (RR MS) before and after initiating interferon (IFN)-beta 1b treatment. There was no significant difference in pretreatment to on-treatment anti-CD3 mAb or Con A-induced proliferation in RR MS patients. There was significantly increased Con A-induced secretion of tumor necrosis factor (TNF)-alpha, IFN-gamma, interleukin (IL)-2, IL-6, and IL-10 and decreased IL-4 secretion in on-treatment compared with pretreatment peripheral blood mononuclear cell samples. However, on-treatment CD3-mediated secretion of TNF-alpha was significantly decreased, and IL-6 secretion was significantly increased compared with pretreatment values. IFN-gamma was also decreased in on-treatment cultures stimulated with anti-CD3 MAb, but these values did not reach statistical significance. Systemic side effects from IFN-beta 1b were associated with increased IL-6 secretion. There were no significant changes in CD3-mediated IL-4, IL-10, transforming growth factor (TGF)-beta, or IL-2 secretion or Con A-induced TGF-beta secretion. IFN-beta 1b (Betaseron) decreases CD3-mediated TNF-alpha secretion but increases another inflammatory cytokine, IL-6, that could potentially counteract its beneficial immunomodulatory effects.
authors.affiliation: Department of Neurology, University of Texas-Houston Health Science Center 77225, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Brod
authors.forename: G D
authors.initials: GD
authors.lastname: Marshall
authors.forename: E M
authors.initials: EM
authors.lastname: Henninger
authors.forename: S
authors.initials: S
authors.lastname: Sriram
authors.forename: M
authors.initials: M
authors.lastname: Khan
authors.forename: J S
authors.initials: JS
authors.lastname: Wolinsky
mesh_terms: D001327:Autoimmune Diseases / Q000378:metabolism / Q000628:therapy*; D003208:Concanavalin A / Q000494:pharmacology; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D009103:Multiple Sclerosis / Q000378:metabolism / Q000628:therapy*; D016853:Muromonab-CD3 / Q000494:pharmacology; D011994:Recombinant Proteins / Q000627:therapeutic use; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D007155:Immunologic Factors; D007376:Interleukin-2; D015850:Interleukin-6; D016853:Muromonab-CD3; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D016753:Interleukin-10; D000068576:Interferon beta-1b; D015847:Interleukin-4; D016899:Interferon-beta; D007371:Interferon-gamma; D000068556:Interferon beta-1a