Interferon-beta is a potent promoter of nerve growth factor production by astrocytes.
Recent clinical evidence has suggested that interferon-beta is efficacious in the treatment of the demyelinating disease, multiple sclerosis. The mechanism of its efficacy remains unclear, and suggested modes of action have focused on immune modulation. Nonimmune effects of interferon-beta may also contribute to its efficacy. Given that astrocytes produce a range of neurotrophic factors, we examined the possibility that interferon-beta could increase the astrocytic production of nerve growth factor (NGF), which has been reported to cause oligodendrocytes to proliferate and to extend their processes; these phenotypes can impact favorably on remyelination. When the recombinant form of mouse interferon-beta was added to mouse astrocyte cultures, a dose-dependent increase in NGF mRNA was obtained. The 40-fold increase in NGF mRNA elicited by 1,000 U/ml interferon-beta was far more potent than that produced by other NGF-elevating agents in this study. In concordance, the protein for NGF was elevated by interferon-beta. The production of NGF by interferon-beta may be relevant to its clinical efficacy in multiple sclerosis. Furthermore, we suggest the potential utility of interferon-beta in Alzheimer's disease.
Boutros
T
T
Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Quebec, Canada.
Croze
E
E
Yong
V W
VW
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D016899:Interferon-beta / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D016716:PC12 Cells; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*
D017077:Culture Media, Conditioned; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016899:Interferon-beta