Modulation of Expression of Genes Involved in the Inflammatory Response by Lipopolysaccharide and Temperature in Cultured Human Astroglial Cells

Abstract

In bacterial sepsis and meningitis, large concentrations of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) correlate directly with morbidity and mortality. This laboratory has reported previously that elevated temperature in the physiologic range is associated with down regulation of IL-1β and TNFα expression in cultured astroglia after lipopolysaccharide (LPS) stimulation. To further investigate the role of elevated temperature in the CNS inflammatory response, the effects of LPS and elevated temperature on the expression of genes that participate in the inflammatory response were determined in cultured transformed human fetal astrocytes and in an astrocytoma cell line. The effect of physiologic temperature elevation on cytokine concentrations in cerebrospinal fluid (CSF) was also investigated in a rabbit meningitis model. The findings indicate that astrocytes express a wide variety of cytokines, growth factors, growth factor receptors, and other genes that could play important roles in CNS inflammation. Furthermore, temperature elevation in the febrile range can lead to alterations in the patterns of expression of many genes involved in the inflammatory response of these cells.