Inhibition of experimental autoimmune encephalomyelitis by a novel small molecular weight proinflammatory cytokine suppressing drug.
Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated, autoimmune disease of the central nervous system (CNS) that serves as a model for various cellular and molecular aspects of the human disease, multiple sclerosis (MS). Although EAE has long been considered a T cell-mediated disease, macrophages play a role in disease pathogenesis and are known to accumulate in the CNS under the control of chemokines. In the present report we demonstrate that mice induced to develop EAE were treated with a small molecular weight molecule that suppresses proinflammatory cytokine production which resulted in significantly decreased clinical EAE, CNS CCL2 expression and CNS macrophage accumulation. These results demonstrate the efficacy of a novel class of therapeutic molecules for CNS demyelinating disease.
Karpus
William J
WJ
Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. w-karpus@northwestern.edu
Reynolds
Nathaneal
N
Behanna
Heather A
HA
Van Eldik
Linda J
LJ
Watterson
D Martin
DM
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology*; D005260:Female; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008970:Molecular Weight; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology; D011724:Pyridazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D012720:Severity of Illness Index
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D011724:Pyridazines; D011743:Pyrimidines; C534736:minozac