Abstract
A novel triptolide derivative (5R)-5-hydroxytriptolide (LLDT-8) has been shown to have potent immunosuppressive activities. Here LLDT-8 was evaluated in experimental autoimmune encephalomyelitis (EAE), the model of multiple sclerosis (MS). LLDT-8 reduced the incidence and severity of EAE, which was associated with the inhibition of the MOG 35-55 lymphocyte recall response, anti-MOG 35-55 T cell responses, interleukin (IL)-2 and interferon (IFN)-gamma production. In vitro, LLDT-8 inhibited primary T cells proliferation, division, IL-2 and IFN-gamma production stimulated with anti-CD3/28. These findings highlight the fact that LLDT-8 prevents EAE by suppressing T cell proliferation and activation, with a potential for treatment of MS.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Cell Proliferation / drug effects
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Diterpenes / administration & dosage
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Diterpenes / chemistry
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Diterpenes / pharmacology
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Diterpenes / therapeutic use*
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Encephalomyelitis, Autoimmune, Experimental / prevention & control*
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Epoxy Compounds
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Female
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Immunosuppressive Agents / administration & dosage
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Immunosuppressive Agents / therapeutic use*
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Lymphocyte Activation / drug effects*
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Lymphocyte Activation / physiology
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Mice
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Mice, Inbred C57BL
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Molecular Sequence Data
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Phenanthrenes / administration & dosage
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Phenanthrenes / pharmacology
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Phenanthrenes / therapeutic use*
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T-Lymphocytes / drug effects*
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T-Lymphocytes / immunology
Substances
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5-hydroxytriptolide
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Diterpenes
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Epoxy Compounds
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Immunosuppressive Agents
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Phenanthrenes
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triptolide