INTERLEUKIN-1-BETA ENHANCES SURVIVAL AND INTERLEUKIN-6 PROTECTS AGAINST MPP(+) NEUROTOXICITY IN CULTURES OF FETAL-RAT DOPAMINERGIC-NEURONS

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-1 beta (IL-1 beta), interleukin-3 (IL-3), or interleukin-6 (IL-6) for the following 2 or 3 DIV with or without 2 mu 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-1 beta 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-1 beta, 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 neuroprotective 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-1 beta and IL-6 on dopaminergic neurons are not mediated by glial proliferation, that IL-1 beta acts as a neurotrophic factor on dopaminergic neurons, and that IL-6 is capable of protecting dopaminergic neurons from the neurotoxicity of MPP(+). (C) 1995 Academic Press, Inc.