Local Overexpression of Interleukin-11 in the Central Nervous System Limits Demyelination and Enhances Remyelination

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.

DOI: 10.1155/2013/685317

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@inproceedings{Maheshwari2013LocalOO, title={Local Overexpression of Interleukin-11 in the Central Nervous System Limits Demyelination and Enhances Remyelination}, author={Anurag Maheshwari and Kris Janssens and Jeroen F. J. Bogie and Chris Van Van den Haute and Tom Struys and I. Lambrichts and Veerle Baekelandt and Piet Stinissen and Jerome J A Hendriks and Helena Slaets and Niels Hellings}, booktitle={Mediators of inflammation}, year={2013} }