Local Overexpression of Interleukin-11 in the Central Nervous System Limits Demyelination and Enhances Remyelination. (30th May 2013)

• Record Type: Journal Article
• Authors: Maheshwari, Anurag; Janssens, Kris; Bogie, Jeroen; Van Den Haute, Chris; Struys, Tom; Lambrichts, Ivo; Baekelandt, Veerle; Stinissen, Piet; Hendriks, Jerome J. A.; Slaets, Helena; Hellings, Niels
• Other Names: Guaza Carmen Academic Editor.
• Is Part Of: Mediators of inflammation. Volume 2013(2013)
• Publication Date: 2013-05-30
• Subjects: Inflammation -- Mediators -- Periodicals; Biological response modifiers -- Periodicals; Inflammation (Pathologie) -- Médiateurs; Immunomodulateurs; Biological response modifiers; Inflammation -- Mediators; Immunology; Autacoids; Immunologic Factors; Cell Adhesion Molecules; Cell Communication; Cytokines; Inflammation; Periodicals; Electronic journals; 616.0473
• DOI: 10.1155/2013/685317
• Languages: English
• ISSNs: 0962-9351

Abstract

Abstract : Demyelination is one of the pathological hallmarks of multiple sclerosis (MS). To date, no therapy is available which directly potentiates endogenous remyelination. Interleukin-11 (IL-11), a member of the gp130 family of cytokines, is upregulated in MS lesions. Systemic IL-11 treatment was shown to ameliorate clinical symptoms in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. IL-11 modulates immune cells and protects oligodendrocytes in vitro . In this study, the cuprizone-induced demyelination mouse model was used to elucidate effects of IL-11 on de- and remyelination, independent of the immune response. Prophylactic-lentiviral- (LV-) mediated overexpression of IL-11 in mouse brain significantly limited acute demyelination, which was accompanied with the preservation of CC1 + mature oligodendrocytes (OLs) and a decrease in microglial activation (Mac-2 + ). We further demonstrated that IL-11 directly reduces myelin phagocytosis in vitro . When IL-11 expressing LV was therapeutically applied in animals with extensive demyelination, a significant enhancement of remyelination was observed as demonstrated by Luxol Fast Blue staining and electron microscopy imaging. Our results indicate that IL-11 promotes maturation of NG2 + OPCs into myelinating CC1 + OLs and may thus explain the enhanced remyelination. Overall, we demonstrate that IL-11 is of therapeutic interest for MS and other demyelinating diseases by limiting demyelination and promoting remyelination.