Cytokine regulation of embryonic rat dopamine and serotonin neuronal survival in vitro.

Interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) are cytokines with pleiotropic effects in the central nervous system (CNS), including an emerging role in neurodevelopment. This study measured the effects of cytokines on the survival of tyrosine hydroxylase (TH) immunoreactive dopamine neurons from the substantia nigra (SN), and 5-hydroxytryptamine (5-HT) immunoreactive serotonin neurons from the rostral raphe (RR), using cultures from embryonic day 14 (E14) rat brain. IL-1beta, IL-6, and TNF-alpha were added to cell cultures at 1, 10 and 100 U/ml. After 3 days in vitro, TH and 5-HT neurons were counted. The survival of 5-HT neurons was significantly reduced by 20-30% at 10 U/ml of IL-6. IL-1beta and TNF-alpha at doses of 1 and 10 U/ml appeared to have a similar effect on the survival of these neurons, but this effect was not statistically significant. Comparable non-significant reductions of survival also occurred for TH neurons at the lower doses of IL-6 and TNF-alpha. In separate experiments, SN and RR cultures were exposed to the cytokines at a higher dose (1000 U/ml), causing a significant 30-40% decrease in the survival of TH neurons, but little or no change in 5-HT neuronal survival. Taken together, these results show that IL-1beta, IL-6, and TNF-alpha can affect developing monoamine neurons at physiologically relevant concentrations, and that high doses differentially inhibit the survival of TH and 5-HT neurons after short exposures.