Neurotrophic effect of hematopoietic cytokines on cholinergic and other neurons in vitro.

We examined the effects of interleukin-3 (IL-3) and other hematopoietic cytokines on the neurotransmitters, neurite formation, and differentiation in cholinergic and other types of neurons. IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor, granulocyte colony-stimulating factor and erythropoietin (Epo) elevated choline acetyltransferase (ChAT) activity in septal cholinergic cell line SN6 as well as in primary cultured septal neurons without increasing protein contents of the cells. These effects were dose-dependent and the optimal doses were not different from those for blood cells. IL-3 had neurite-promoting activity but GM-CSF had no such effect. Both IL-3 and GM-CSF decreased intracellular acetylcholine concentration, and elevated glutamic acid decarboxylase and intracellular GABA in septal neuronal cultures. Epo elevated monoamines in PC12 cells. These effects are thought to result from direct action through their specific receptors in neurons, because (i) anti-IL-3-receptor antibody abolished the ChAT activity in septal neurons increased by IL-3; (ii) mRNA and immunoreactivity for beta subunits of IL-3 receptors were expressed in septal cholinergic neurons and (iii) presence of receptors for GM-CSF and Epo in neurons has been reported. Our observation and others strongly support that neural-immune interactions are important not only in the defense mechanism in the nervous system but also in the development, differentiation and function of neurons.