CYTOKINE-INDUCED PROGRAMMED DEATH OF CULTURED SYMPATHETIC NEURONS

Programmed cell death (PCD) of sympathetic neurons is inhibited by ner ve growth factor. However, factors that induce PCD of these cells are unknown. Leukemia inhibitory factor (LIF) and ciliary neurotrophic fac tor, neuropoietic cytokines known to regulate sympathetic neuron gene expression, were examined for effects on survival of cultured sympathe tic neurons. Treatment with LIF or ciliary neurotrophic factor caused neuronal death in a dose-dependent fashion. Inhibition of RNA or prote in synthesis, or treatment with potassium, all of which prevent PCD af ter nerve growth factor deprivation, prevented LIF-induced death. The morphologic and ultrastructural characteristics of the neuronal death induced by LIF and by nerve growth factor deprivation were similar. Fu rthermore, LIF treatment resulted in DNA fragmentation with a characte ristic ''ladder'' on Southern blot analysis. These observations sugges t that neuron numbers may be regulated by factors which initiate PCD, as well as by factors which prevent it.