Additive effects of combination treatment with anti-inflammatory and neuroprotective agents in experimental autoimmune encephalomyelitis.
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.
Du
Sienmi
S
University of California, Los Angeles, Department of Neurology, UCLA Multiple Sclerosis Program, 635 Charles E Young Drive South, Neuroscience Research Building 1, Room 479, Los Angeles, CA 90095, United States.
Sandoval
Francisco
F
Trinh
Pauline
P
Voskuhl
Rhonda R
RR
D000704:Analysis of Variance; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination / Q000379:methods; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006023:Glycoproteins; D007155:Immunologic Factors / Q000494:pharmacology*; D039041:Integrin alpha4beta1 / Q000378:metabolism; D016899:Interferon-beta / Q000494:pharmacology*; D008164:Luminescent Proteins / Q000235:genetics; D008264:Macrophages / Q000187:drug effects; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020556:Neutrophil Infiltration / Q000187:drug effects; D009570:Nitriles / Q000627:therapeutic use*; D010446:Peptide Fragments; D011422:Propionates / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology
C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D015703:Antigens, CD; D000943:Antigens, Differentiation; D016207:Cytokines; D006023:Glycoproteins; D007155:Immunologic Factors; D039041:Integrin alpha4beta1; D008164:Luminescent Proteins; D004676:Myelin Basic Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D018696:Neuroprotective Agents; D009570:Nitriles; D010446:Peptide Fragments; D011422:Propionates; C036763:monocyte-macrophage differentiation antigen; C445081:myelin oligodendrocyte glycoprotein (35-55); D016899:Interferon-beta; D020780:Matrix Metalloproteinase 9