1. Interferon-beta 1b treatment decreases tumor necrosis factor-alpha and increases interleukin-6 production in multiple sclerosis.
- Author
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Brod SA, Marshall GD Jr, Henninger EM, Sriram S, Khan M, and Wolinsky JS
- Subjects
- Autoimmune Diseases metabolism, Concanavalin A pharmacology, Humans, Interferon beta-1a, Interferon beta-1b, Interferon-gamma metabolism, Interleukin-10 metabolism, Interleukin-2 metabolism, Interleukin-4 metabolism, Lymphocyte Activation drug effects, Multiple Sclerosis metabolism, Muromonab-CD3 pharmacology, Recombinant Proteins therapeutic use, T-Lymphocytes, Cytotoxic immunology, T-Lymphocytes, Cytotoxic metabolism, Autoimmune Diseases therapy, Immunologic Factors therapeutic use, Interferon-beta therapeutic use, Interleukin-6 metabolism, Multiple Sclerosis therapy, T-Lymphocytes, Cytotoxic drug effects, Tumor Necrosis Factor-alpha metabolism
- 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.
- Published
- 1996
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