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Katarzyna Biernacki, PhD; Jack P. Antel, MD; Manon Blain; Sridar Narayanan, PhD; Douglas L. Arnold, MD; Alexandre Prat, MD, PhD, FRCPC

Arch Neurol. 2005;62:563-568.

Background  Interferon beta therapy has been shown to reduce the rate of clinical relapse and the frequency of magnetic resonance imaging–defined T2- weighted lesions in patients with multiple sclerosis (MS). When given early, interferon beta also reduces the rate of development of brain atrophy and improves axonal integrity. Nerve growth factor (NGF) can retard the severity and course of experimental allergic encephalomyelitis.

Objective  To determine whether interferon beta effects on patients with MS could be related to modulation of neurotrophin production within the central nervous system.

Design  We studied neurotrophin production by human glial and brain endothelial cells in response to coculture with MS patient–derived lymphocytes, and correlated levels of NGF secretion with clinical and magnetic resonance imaging–defined markers of disease.

Results  We demonstrate that production of NGF by human brain microvascular endothelial cells is triggered by interaction with T lymphocytes derived from MS patients. No such response was observed using human adult microglia or human fetal astrocytes. Nerve growth factor production by endothelial cells was potentiated by pretreating lymphocytes with interferon beta in vitro, and by using lymphocytes derived from MS patients treated with interferon beta in vivo. By using this assay, we show that levels of NGF induced by lymphocytes from MS patients inversely correlate with magnetic resonance imaging measures of brain atrophy and axonal injury.

Conclusion  These findings suggest that interferon beta–mediated production of NGF at the level of the blood-brain barrier, whether acting as an immunomodulator or directly on neural cells, is another potential mechanism contributing to the magnetic resonance imaging–defined effect of interferon beta on brain atrophy when given early in the course of MS.

Author Affiliations: Neuroimmunology Unit (Ms Blain and Drs Biernacki, Antel, and Prat) and McConnell Brain Imaging Center (Drs Narayanan and Arnold), Montreal Neurological Institute, McGill University; and Multiple Sclerosis Clinic, Hôpital Notre-Dame, Université de Montréal (Dr Prat), Montreal, Quebec.

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