CNTF is a major protective factor in demyelinating CNS disease: a neurotrophic cytokine as modulator in neuroinflammation.
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). So far, immunological mechanisms responsible for demyelination have been the focus of interest. However, mechanisms regulating axon maintenance as well as glial precursor-cell proliferation and oligodendrocyte survival might also influence disease outcome. The cytokine ciliary neurotrophic factor (CNTF), which was originally identified as a survival factor for isolated neurons, promotes differentiation, maturation and survival of oligodendrocytes. 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-alpha, suggesting that endogenous CNTF may counterbalance this effect of TNF-alpha (ref. 7). Here we identify a factor that modulates, in an inflammatory environment, glial cell survival and is an outcome determinant of EAE.
Linker
Ralf A
RA
Clinical Research Group for Multiple Sclerosis, Department of Neurology, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
Mäurer
Mathias
M
Gaupp
Stefanie
S
Martini
Rudolf
R
Holtmann
Bettina
B
Giess
Ralf
R
Rieckmann
Peter
P
Lassmann
Hans
H
Toyka
Klaus V
KV
Sendtner
Michael
M
Gold
Ralf
R
D000818:Animals; D020934:Ciliary Neurotrophic Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016207:Cytokines / Q000502:physiology; D003711:Demyelinating Diseases / Q000517:prevention & control*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology*; D007249:Inflammation / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000517:prevention & control*; D009414:Nerve Growth Factors / Q000502:physiology*
D020934:Ciliary Neurotrophic Factor; D016207:Cytokines; D009414:Nerve Growth Factors