IL-11 and remyelination


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 signs 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. 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.

Interleukin-11 is a cytokine that is shown here to promote remyelination. However, it has lots of other functions including development of white blood cells and bones. So whilst it may be a new potential therapy these multiple effects may influence whether it will be developed. Many of the molecules found to influence remyelination also have other targets and  this could be their achilles heel too

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    This new model based on insertion of Diptheria toxin – A locus is proposed by the authors to be superior to the cuprizone induced demyelinating model used in the paper when studying candidate molecules for re-myelination. Authors state that DTA is localized in OPCs and therefore acts exclusively on these myelinating cells. Do believe that one model is superior when studying re-myelination? Would research be accelerated if the best model was utilized?

  • Thanks the new model was published in 2010 and has not caught on yet. There have been a few mice which do this so you can kill oligodendrocytes. Each model has its advantages and disadvantages. The models generally remyelinate which is the default, so drugs then tend to support something that will happen anyway.

    Having long term demyelination would be good model and one where there is gliosis and inflammation so more MS like, best still . EAE could be useful but what you need to go if get the demyelination and then turn off the immune response. We published the methods of how to do that.

    There are quite a few targets it will be a case of just try them and see what happens but if you do not deal with the inflammatory response then it will be a waste of time.

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