Effect of immunomodulatory drugs on in vitro production of brain-derived neurotrophic factor.
Multiple sclerosis (MS), a disease of presumably autoimmune aetiology, is characterized by inflammation, demyelination and axonal degeneration in the central nervous system. Current treatment concepts target the inflammatory activity, reducing the number of relapses and inflammatory lesions on magnetic resonance imaging as well as the proinflammatory cytokine production in blood lymphocytes. Recently, the neuroprotective aspect of inflammation has been documented and is thought to be mediated by neurotrophins, like brain-derived neurotrophic factor (BDNF). The question whether the in vitro BDNF production in MS patients and healthy controls is influenced by the immunomodulatory agents interferon beta (IFN-beta) and immunoglobulin G (Ig) is addressed. A significantly increased BDNF production in MS patients was found compared with normal controls (mean +/- SD: 492 +/- 172 pg/mL versus 217 +/- 55 pg/mL, P < 0.001). IFN-beta and low-dose Ig had no effect on BDNF production, whereas high-dose Ig reduced in vitro BDNF production in MS patients significantly (to 409 +/- 125 pg/mL, P = 0.001). These in vitro findings might indicate that Igs in high doses potentially interfere with neuroprotective mechanisms despite their potent anti-inflammatory properties.
Petereit
H F
HF
Department of Neurology, University of Cologne, D-50924 Cologne, Germany. hela.petereit@medizin.uni-koeln.de
Lindemann
H
H
Schoppe
S
S
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D066298:In Vitro Techniques; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000276:immunology*; D015213:Neuroimmunomodulation / Q000276:immunology
D000276:Adjuvants, Immunologic; D019208:Brain-Derived Neurotrophic Factor; D007074:Immunoglobulin G; D016899:Interferon-beta; D007371:Interferon-gamma