Neural-immune interactions in sympathetic ganglia.

Effects of immune cytokines on neuronal gene expression have recently been examined in cultured superior cervical (sympathetic) ganglia, a widely used model system for the study of neurotransmitter plasticity. Following deafferentation and explantation into culture, interleukin-1 causes an up-regulation of the neuropeptide substance P as well as of choline acetyltransferase. Tumor necrosis factor-alpha has a similar, though less potent, action. Since interleukin-1 was ineffective in raising the concentration of substance P in pure neuronal cultures, the existence of a non-neuronally derived intermediate was postulated and found to exist in interleukin-1-conditioned medium. Antibody neutralization of either nerve growth factor or ciliary neurotrophic factor failed to affect the ability of interleukin-1 to induce substance P. Inhibition of prostaglandin biosynthesis was equally ineffective. However, immunoprecipitation of leukemia inhibitory factor from interleukin-1-conditioned medium eliminated substance-P-inducing activity, suggesting leukemia inhibitory factor as a possible interleukin-1-induced intermediate. The ability of interleukin-1 to induce leukemia inhibitory factor mRNA strengthens this conclusion. Glucocorticoid hormones block the interleukin-1 induction of leukemia inhibitory factor, which explains why they block the interleukin-1 induction of substance P.