Production of brain-derived neurotrophic factor by mononuclear cells of patients with multiple sclerosis treated with glatiramer acetate, interferon-beta 1a, and high doses of immunoglobulins

¹ Neurologic Clinic, Department of Medical and Surgical Specialties and Public Health, University of Perugia, Perugia 06158, Italy
² Center for the Study of Multiple Sclerosis, Ospedale S Antonio Abate, Via Pastori 4, I-21013 Gallarate (VA), Italy

^* To whom correspondence should be addressed.

	Abstract

Sixty, relapsing remitting (RR) multiple sclerosis (MS) patients, who underwent treatment with glatiramer acetate (GA), interferon (IFN)-beta 1a, and immunoglobulins (Igs) (20 per treatment group), were assessed for levels of brain-derived neurotrophic factor (BDNF) in the supernatants of unstimulated and stimulated peripheral blood mononuclear cells (PBMCs) in the first year of treatment. Phytohemagglutinin (PHA), anti-OKT3 antibody, myelin basic protein (MPB) and GA were used as stimuli. Cytokine responses by ELISPOT and lymphoproliferative responses were also assessed. The GA-treated MS patient group showed a progressive increase in BDNF levels, from baseline to month three; thereafter, the levels remained stable and significantly greater compared with baseline and controls (ANOVA=P<0.001). IFN-beta 1a had no effect on BDNF production, whereas Igs induced a slight decrease (ANOVA=P<0.04). ELISPOT analysis revealed a significant decrease of IFN-, an increase of interleukin (IL)-4 and IL-5 in GA-treated MS patients, and an increase of IL-10 in patients treated with IFN-beta 1a and GA. No significant correlation was found between BDNF secretion in the supernatants of PBMCs and cytokine response, lesional load, and measures of atrophy. Increased BDNF production related to GA treatment can have implications for understanding the mechanism of action of this immunomodulatory agent, in light of evidence suggesting its effects in promoting neuroprotective immunity in MS patients; however, a clinically measurable effect, especially in terms of an impact on actual disease progression, remains to be established.

Key Words: brain-derived neurotrophic factor, glatiramer acetate, immunoglobulins, interferon-beta 1a, multiple sclerosis, peripheral blood mononuclear cells

First published on January 29, 2007, doi:10.1177/1352458506070146

Multiple Sclerosis 2007;13:313.

A more recent version of this article appeared on April 1, 2007


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