Abstract
Interferon-beta regimens for immune-mediated diseases, such as multiple sclerosis (MS), have not been compared regarding their biological effects. In this randomized, parallel-group, placebo-controlled study, cytokine secretion by mitogen-stimulated PBMCs and serum response markers were assessed in volunteers receiving subcutaneous recombinant IFN beta-1a (Rebif, Ares-Serono) 22 microg once a week (QW), 22 microg three times a week, 66 microg QW, or placebo. The production of IL-1beta, IL-6, IFN-gamma, TNF-alpha and TNF-beta markedly decreased during 24-48 h after each injection, with limited dose-dependency and no evidence of tolerance or effect augmentation over 1 month. IL-10 secretion remained unchanged. The increase in serum beta2-microglobulin, neopterin and 2-5A-synthetase was more sustained. Thus, IFN-beta-induced immunomodulation in vivo strongly depends on the administration schedule, the time-integrated effect being 2-3 times greater when a same weekly dose is divided in three injections.
Publication types
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Clinical Trial
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Comparative Study
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Randomized Controlled Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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2',5'-Oligoadenylate Synthetase / blood
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Adult
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Dose-Response Relationship, Immunologic
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Drug Administration Schedule
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Fatigue / chemically induced
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Fever / chemically induced
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Headache / chemically induced
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Humans
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Immunologic Factors / administration & dosage*
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Immunologic Factors / adverse effects
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Immunologic Factors / therapeutic use
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Interferon beta-1a
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Interferon-beta / administration & dosage*
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Interferon-beta / adverse effects
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Interferon-beta / therapeutic use
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Interferon-gamma / metabolism
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Interleukin-1 / metabolism
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Interleukin-6 / metabolism
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Lymphocyte Activation / drug effects*
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Lymphokines / metabolism*
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Lymphotoxin-alpha / metabolism
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Male
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Neopterin / blood
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Recombinant Proteins / administration & dosage
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Recombinant Proteins / adverse effects
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Recombinant Proteins / therapeutic use
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Safety
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T-Lymphocytes / drug effects
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T-Lymphocytes / metabolism*
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Tumor Necrosis Factor-alpha / metabolism
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beta 2-Microglobulin / analysis
Substances
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Immunologic Factors
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Interleukin-1
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Interleukin-6
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Lymphokines
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Lymphotoxin-alpha
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Recombinant Proteins
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Tumor Necrosis Factor-alpha
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beta 2-Microglobulin
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Neopterin
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Interferon-beta
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Interferon-gamma
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2',5'-Oligoadenylate Synthetase
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Interferon beta-1a