Interferon beta in multiple sclerosis.
Interferon beta 1B (IFNbeta1b) lessens multiple sclerosis (MS) attack frequency and accumulating disease burden as assessed by MRI. The agent is an immune system modulator. The immune response in MS is thought to involve a delayed-type hypersensitivity (DTH) response mediated by Th1 type T cells. IFNbeta1b lessens expression of MHC-class II proteins on blood monocytes but only after a delay. This action could impede antigen presentation. Expression of the B7-1 costimulatory molecule on B cells is also reduced in MS patients receiving IFNbeta1b. Downregulation of B7-1 expression could inhibit Th1 cell activation. IFNbeta1b exerts an antiproliferative effect on T cells, an action which could lessen the magnitude of Th1 cell responses. Several cytokines are secreted by Th1 cells or by the monocytes/macrophages that they activate. IL-2, IFNgamma, lymphotoxin, and tumor necrosis factor (TNF) are made by activated Th1 type T cells, IL-1, and TNF by activated macrophages. IFNbeta1b increases IL-2 production in vitro but decreases production of IFNgamma, LT, and TNF. If these same effects occur in vivo, a substantial attenuation of the effector arm of DTH response would be anticipated. IFNbeta1b has no known effect on Th2 type T cells. It increases CD8 cell function including that of CD8 suppressor cells, the function of which is known to be deficient when MS is active. Production of the suppressive cytokines IL-10 and transforming growth factor beta-1 is increased in vitro by IFNbeta1b. Taken in sum, the immunomodulatory actions of IFNbeta1b acting in concert would be expected to attenuate DTH responses and exert a beneficial effect in MS, as is found.
Arnason
B G
BG
Pritzker School of Medicine and the Brain Research Institute, University of Chicago, Illinois 60637, USA.
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000209:etiology; D002493:Central Nervous System Diseases / Q000209:etiology; D006801:Humans; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000009:adverse effects / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000276:immunology / Q000628:therapy*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000276:Adjuvants, Immunologic; D011994:Recombinant Proteins; D000068576:Interferon beta-1b; D016899:Interferon-beta; D000068556:Interferon beta-1a