Abstract
IL-33 is a recently described member of the IL-1 family that has been reported to have a pathogenic role in several inflammatory diseases. In this study, we evaluated the role of IL-33 in a murine model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). We showed that the expression of IL-33 and its receptor, ST2, was markedly elevated in the spinal cord of mice during myelin oligodendrocyte glycoprotein (MOG)(35-55) peptide-induced EAE. Administration of a blocking anti-IL-33 antibody in mice of EAE during the induction phase significantly inhibited the onset and severity of EAE and reduced MOG(35-55)-induced IFN-γ and IL-17 production. In contrast, treatment with recombinant IL-33 worsened the disease course of EAE in association with increased induction of both IFN-γ and IL-17. Furthermore, anti-IL-33 treatment caused a remarkable decrease in expression of IL-17, IFN-γ, T-bet and RORγt, and an upregulation of IL-10 and TGF-β in the spinal cord of EAE mice. These results demonstrate that endogenous IL-33 plays a pivotal role in the pathogenesis of EAE and indicate that blockade of IL-33 has a significant protective effect against EAE.
Copyright © 2012 Elsevier B.V. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Analysis of Variance
-
Animals
-
Antibodies / therapeutic use*
-
Cytokines / metabolism
-
Disease Models, Animal
-
Dose-Response Relationship, Immunologic
-
Encephalomyelitis, Autoimmune, Experimental / chemically induced
-
Encephalomyelitis, Autoimmune, Experimental / drug therapy*
-
Encephalomyelitis, Autoimmune, Experimental / pathology
-
Enzyme-Linked Immunosorbent Assay
-
Female
-
Gene Expression Regulation / drug effects
-
Glycoproteins / adverse effects
-
Interleukin-1 Receptor-Like 1 Protein
-
Interleukin-33
-
Interleukins / genetics
-
Interleukins / immunology*
-
Interleukins / metabolism*
-
Mice
-
Mice, Inbred C57BL
-
Myelin-Oligodendrocyte Glycoprotein
-
Peptide Fragments / adverse effects
-
RNA, Messenger / metabolism
-
Receptors, Interleukin / genetics
-
Receptors, Interleukin / metabolism
-
Spinal Cord / drug effects
-
Spinal Cord / metabolism
-
T-Lymphocytes, Helper-Inducer / drug effects
-
T-Lymphocytes, Helper-Inducer / immunology
-
Time Factors
Substances
-
Antibodies
-
Cytokines
-
Glycoproteins
-
Il1rl1 protein, mouse
-
Il33 protein, mouse
-
Interleukin-1 Receptor-Like 1 Protein
-
Interleukin-33
-
Interleukins
-
Myelin-Oligodendrocyte Glycoprotein
-
Peptide Fragments
-
RNA, Messenger
-
Receptors, Interleukin
-
myelin oligodendrocyte glycoprotein (35-55)