CNTF is a major protective factor in demyelinating CNS disease: A neurotrophic cytokine as modulator in neuroinflammation
Ralf A. Linker1, Mathias Mäurer1, Stefanie Gaupp1, Rudolf Martini2, Bettina Holtmann3, Ralf Giess1, Peter Rieckmann1, Hans Lassmann4, Klaus V. Toyka1, Michael Sendtner3
& Ralf Gold1
1
Clinical Research Group for Multiple Sclerosis, Department of Neurology, Julius-Maximilians-Universität Würzburg, Würzburg, Germany
2
Section of Developmental Neurobiology, Department of Neurology, Julius-Maximilians-Universität Würzburg, Würzburg, Germany
3
Department of Clinical Neurobiology, Julius-Maximilians-Universität, Würzburg, Germany
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS)1. So far, immunological mechanisms responsible for demyelination have been the focus of interest2. However, mechanisms regulating axon maintenance as well as glial precursor-cell proliferation and oligodendrocyte survival might also influence disease outcome3. The cytokine ciliary neurotrophic factor (CNTF), which was originally identified as a survival factor for isolated neurons, promotes differentiation, maturation and survival of oligodendrocytes4,
5,
6. To investigate the role of endogenous CNTF in inflammatory demyelinating disease, we studied myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) in CNTF-deficient and wild-type C57BL/6 mice. Disease was more severe in CNTF-deficient mice and recovery was poor, with a 60% decrease in the number of proliferating oligodendrocyte precursor cells (OPCs) and a more than 50% increase in the rate of oligodendrocyte apoptosis. In addition, vacuolar dystrophy of myelin and axonal damage were more severe in CNTF-deficient mice. These specific pathological features could be prevented by treatment with an antiserum against tumor necrosis factor-, suggesting that endogenous CNTF may counterbalance this effect of TNF- (ref. 7). Here we identify a factor that modulates, in an inflammatory environment, glial cell survival and is an outcome determinant of EAE.
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, suggesting that endogenous CNTF may counterbalance this effect of TNF-
