Influence of neurons on lipopolysaccharide-stimulated production of nitricoxide and tumor necrosis factor-alpha by cultured glia

Cerebral inflammation often originates in a region where neuronal death occ urs and thereafter slowly spreads outward. This study aimed to elucidate th e roles of neurons in modulating the production of inflammatory factors sti mulated by the bacterial endotoxin lipopolysaccharide (LPS). Culturing neur ons with mixed glia reduced nitrite and tumor necrosis factor-alpha (TNF-al pha) production compared to cultures with only mixed glia, and shifted the dose-response curve to the right. The decreased nitrite and TNF-alpha produ ction were not due to the cytotoxicity of LPS. Immunocytochemical analysis of glia-neuron co-cultures revealed the morphological changes in the activa ted microglia. Culturing PC12 cells with rat mixed-glia also reduced nitrit e production. The influence of neurons on glial inflammation was partly due to the cell-cell contacts between neurons and glia via neural cell adhesio n molecules (NCAM) because NCAM significantly reduced LPS-stimulated nitrit e production. These results demonstrate that neurons reduce the production of inflammatory factors by glia. Since cerebral inflammation is important i n many neurological disorders, this study might provide insight about the r ole of glia-neuron interactions in inflammatory responses in the brain. (C) 2000 Elsevier Science B.V. All rights reserved.