Interleukin-1β Enhances Survival and Interleukin-6 Protects against MPP + Neurotoxicity in Cultures of Fetal Rat Dopaminergic Neurons

• Published in: Experimental neurology Vol. 136; no. 1; pp. 44 - 52
• Main Authors: Akaneya, Yukio, Takahashi, Mitsuo, Hatanaka, Hiroshi
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01-11-1995; Elsevier
• Subjects: 1-Methyl-4-phenylpyridinium - pharmacology; Animals; Biological and medical sciences; Cell Survival - drug effects; Cells, Cultured - drug effects; Central Nervous System - drug effects; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dopamine - metabolism; Dose-Response Relationship, Drug; Female; Immunohistochemistry; Interleukin-1 - pharmacology; Interleukin-6 - pharmacology; Medical sciences; Mesencephalon - drug effects; Mesencephalon - immunology; Neurology; Neurons - drug effects; Pregnancy; Rats; Rats, Wistar; Cell culture; Nervous system diseases; Rat; Cytokine; Rodentia; Central nervous system; Parkinson disease; Interleukin 1β; Midbrain; Neuroprotective agent; Cerebral disorder; Interleukin 6; Vertebrata; Mammalia; Animal; Central nervous system disease; Neurotoxin; Fetus; Dopaminergic neuron; Degenerative disease; Extrapyramidal syndrome
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1006/exnr.1995.1082

To investigate the relationships between the central nervous system and interleukins, ventral mesencephalic cells from embryonic 17-day-old rats were cultured for 3 days
in vitro (DIV) and exposed to interleukin 1β (IL-1β), interleukin-3 (IL-3), or interleukin-6 (IL-6) for the following 2 or 3 DIV with or without 2 μ
M 1-methyl-4-phenylpyridinium (MPP
+). Thus, the survival of and the MPP
+ neurotoxicity against the dopaminergic neurons immunostained with anti-tyrosine hydroxylase antibody were examined. For the survival studies, IL-1β has been shown to have a survival-promoting effect on dopaminergic neurons. This effect is initiated at a concentration between 0.1 and 1 ng/ml. In contrast to the effect of IL-1β IL-3 and IL-6 failed to increase the survival of dopaminergic neurons. In MPP
+ neurotoxicity analysis, only IL-6 among the three interleukins studied here has been shown to attenuate the MPP
+ neurotoxicity against dopaminergic neurons in a dose-dependent manner; this neuro-protective action is apparent at a concentration of 10 ng/ml. In addition, these three interleukins did not promote glial proliferation. These findings suggest that the effects of IL-1β and IL-6 on dopaminergic neurons are not mediated by glial proliferation, that IL-1β acts as a neurotrophic factor on dopaminergic neurons, and that IL-6 is capable of protecting dopaminergic neurons from the neurotoxicity of MPP
+.