Selegiline as immunostimulant--a novel mechanism of action?
In clinical studies the MAO-B inhibitor selegiline appears to slow the progression of neurological deficits in Parkinson's disease (PD) and the cognitive decline in Alzheimer's disease (AD). The mechanisms of action remain unclear. Several lines of evidence indicate an immune-mediated pathophysiology of PD and AD. According to animal trials, selegiline increases the survival rate of immune suppressed mice. Stimulation of the immune response to bacterial or viral infection or in chronic inflammatory processes in managed by an increased synthesis of the cytokines interleukin-1 beta (IL-1 beta) and subsequent interleukin-6 (IL-6). Outcome of viral or bacterial infections in the brain highly correlates with levels of the cytotoxic cytokine tumor-necrosis-factor-alpha (TNF). The aim of our study was to characterize the influence of selegiline on the biosynthesis of IL-1 beta, IL-6 and TNF in human peripheral blood mononuclear cells (PBMC) from healthy blood donors. After isolation and washing PBMC were cultured without and with selegiline in three different concentrations (0.01 mumol/l, 0.001 mumol/l, 0.0001 mumol/l) in a humidified atmosphere (7% CO2). Then cultures were centrifuged and supernatants were collected for IL-1 beta, IL-6 and TNF ELISA-assays. Treatment of cultured PBMC with various concentrations induced an increased synthesis of IL-1 beta (ANOVA F = 9.703, p = 0.0007), IL-6 (ANOVA F = 20.648, p = 0.0001) and a reduced production of TNF (ANOVA F = 3.770, p = 0.040). These results indicate, that the influence of selegiline on the cytokine biosynthesis may also contribute to its putative neuroprotective properties.
Müller
T
T
Department of Neurology, St. Josef-Hospital, University of Bochum, Federal Republic of Germany.
Kuhn
W
W
Krüger
R
R
Przuntek
H
H
D000276:Adjuvants, Immunologic; D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D012642:Selegiline / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000276:Adjuvants, Immunologic; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008996:Monoamine Oxidase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D012642:Selegiline