Abstract
We studied the effects of combination treatment with an anti-inflammatory agent, interferon (IFN)-beta, and a putative neuroprotective agent, an estrogen receptor (ER)-beta ligand, during EAE. Combination treatment significantly attenuated EAE disease severity, preserved axonal densities in spinal cord, and reduced CNS inflammation. Combining ERbeta treatment with IFNbeta reduced IL-17, while it abrogated IFNbeta-mediated increases in Th1 and Th2 cytokines from splenocytes. Additionally, combination treatment reduced VLA-4 expression on CD4+ T cells, while it abrogated IFNbeta-mediated decreases in MMP-9. Our data demonstrate that combination treatments can result in complex effects that could not have been predicted based on monotherapy data alone.
Copyright 2009 Elsevier B.V. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Analysis of Variance
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Animals
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Antigens, CD / metabolism
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Antigens, Differentiation / metabolism
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Cytokines / metabolism
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Disease Models, Animal
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Drug Therapy, Combination / methods
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Encephalomyelitis, Autoimmune, Experimental / chemically induced
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Encephalomyelitis, Autoimmune, Experimental / drug therapy*
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Female
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Glycoproteins
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Immunologic Factors / pharmacology*
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Integrin alpha4beta1 / metabolism
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Interferon-beta / pharmacology*
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Luminescent Proteins / genetics
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Macrophages / drug effects
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Matrix Metalloproteinase 9 / metabolism
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Mice
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Mice, Transgenic
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Myelin Basic Protein / metabolism
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Myelin-Oligodendrocyte Glycoprotein
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Neuroprotective Agents / therapeutic use*
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Neutrophil Infiltration / drug effects
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Nitriles / therapeutic use*
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Peptide Fragments
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Propionates / therapeutic use*
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Severity of Illness Index
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Spinal Cord / drug effects
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Spinal Cord / pathology
Substances
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2,3-bis(4-hydroxyphenyl)-propionitrile
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Antigens, CD
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Antigens, Differentiation
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Cytokines
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Glycoproteins
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Immunologic Factors
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Integrin alpha4beta1
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Luminescent Proteins
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Myelin Basic Protein
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Myelin-Oligodendrocyte Glycoprotein
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Neuroprotective Agents
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Nitriles
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Peptide Fragments
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Propionates
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monocyte-macrophage differentiation antigen
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myelin oligodendrocyte glycoprotein (35-55)
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Interferon-beta
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Matrix Metalloproteinase 9