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

To investigate the relationships between the central nervous system an d interleukins, ventral mesencephalic cells from embryonic 17-day-old rats were cultured for 3 days in vitro (DIV) and exposed to interleuki n-1 beta (IL-1 beta), interleukin-3 (IL-3), or interleukin-6 (IL-6) fo r the following 2 or 3 DIV with or without 2 mu M 1-methyl-4-phenylpyr idinium (MPP(+)). Thus, the survival of and the MPP(+) neurotoxicity a gainst the dopaminergic neurons immunostained with anti-tyrosine hydro xylase antibody were examined. For the survival studies, IL-1 beta has been shown to have a survival-promoting effect on dopaminergic neuron s. 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 incr ease the survival of dopaminergic neurons. In MPP(+) neurotoxicity ana lysis, only IL-6 among the three interleukins studied here has been sh own to attenuate the MPP(+) neurotoxicity against dopaminergic neurons in a dose-dependent manner; this neuroprotective action is apparent a t a concentration of 10 ng/ml. In addition, these three interleukins d id not promote glial proliferation. These findings suggest that the ef fects of IL-1 beta and IL-6 on dopaminergic neurons are not mediated b y glial proliferation, that IL-1 beta acts as a neurotrophic factor on dopaminergic neurons, and that IL-6 is capable of protecting dopamine rgic neurons from the neurotoxicity of MPP(+). (C) 1995 Academic Press , Inc.