NEUROTROPHIC EFFECT OF HEMATOPOIETIC CYTOKINES ON CHOLINERGIC AND OTHER NEURONS IN-VITRO

We examined the effects of interleukin-3 (IL-3) and other hematopoieti c cytokines on the neurotransmitters, neurite formation, and different iation in cholinergic and other types of neurons. IL-3, granulocyte-ma crophage colony-stimulating factor (GM-CSF), macrophage colony-stimula ting factor, granulocyte colony-stimulating factor and erythropoietin (Epo) elevated choline acetyltransferase (ChAT) activity in septal cho linergic cell line SN6 as well as in primary cultured septal neurons w ithout increasing protein contents of the cells. These effects were do se-dependent and the optimal doses were not different from those for b lood cells. IL-3 had neurite-promoting activity but GM-CSF had no such effect. Both IL-3 and GM-CSF decreased intracellular acetylcholine co ncentration, and elevated glutamic acid decarboxylase and intracellula r GABA in septal neuronal cultures. Epo elevated monoamines in PC12 ce lls. These effects are thought to result from direct action through th eir specific receptors in neurons, because (i) anti-IL-3-receptor anti body abolished the ChAT activity in septal neurons increased by IL-3; (ii) mRNA and immunoreactivity for beta subunits of IL-3 receptors wer e expressed in septal cholinergic neurons and (iii) presence of recept ors for GM-CSF and Epo in neurons has been reported. Our observation a nd others strongly support that neural-immune interactions are importa nt not only in the defense mechanism in the nervous system but also in the development, differentiation and function of neurons.