Abstract
Based on gene expression data, we tested the P8A-CCL2 variant of the chemokine CCL2, able to interfere with the chemotactic properties of the parental molecule, in relapsing-remitting (RR)-EAE SJL. Only preventive treatment significantly delayed disease onset in a dose dependent manner. P8A-CCL2 administration, however, decreased demyelination, axonal loss and number of CNS infiltrating T cells and macrophages. Immunological analysis revealed that P8A-CCL2 does not act on Ag-specific T cell proliferation and does not interfere with the differentiation of IFNgamma-releasing effectors T cells. These results suggest that the therapeutic mechanism of P8A-CCL2 may rely on interference with immune cell recruitment.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Animals
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Cell Proliferation / drug effects
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Chemokine CCL2 / chemical synthesis
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Chemokine CCL2 / pharmacology*
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Chemokine CCL2 / therapeutic use
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Chemotaxis, Leukocyte / drug effects*
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Chemotaxis, Leukocyte / immunology
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Encephalomyelitis, Autoimmune, Experimental / drug therapy*
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Encephalomyelitis, Autoimmune, Experimental / immunology*
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Encephalomyelitis, Autoimmune, Experimental / physiopathology
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Female
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Humans
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Immunologic Factors / pharmacology
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Immunologic Factors / therapeutic use
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Interferon-gamma / metabolism
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Macrophages / drug effects
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Macrophages / immunology
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Male
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Mice
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Mice, Inbred C57BL
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Middle Aged
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Myelin Sheath / drug effects*
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Myelin Sheath / immunology
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Myelin Sheath / pathology
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Neuroprotective Agents / pharmacology
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Neuroprotective Agents / therapeutic use
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology
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Wallerian Degeneration / drug therapy
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Wallerian Degeneration / immunology
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Wallerian Degeneration / physiopathology
Substances
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Ccl2 protein, mouse
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Chemokine CCL2
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Immunologic Factors
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Neuroprotective Agents
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Interferon-gamma