Inhibition of astrocyte TNFα expression by extracellular potassium

TNF alpha and IL-6 are cytokines of great interest, given the numerous biological activities and the documented expression in several central nervous system (CNS) pathologies. In this report, we have examined cultures of IL-1- or IL-1/IFN gamma -activated human fetal astrocytes as a model to study mechanisms of cytokine regulation in the inflamed CNS. Since one of the major functions of astrocytes is spatial buffering of K+ ions, we examined the effect of high extracellular KCl on astrocyte cytokine expression by ribonuclease protection assay and ELISA. Results demonstrate that astrocyte TNF alpha production was potently inhibited by K+ with 44 and 89% inhibition at 25 and 55 mM K+, respectively. In contrast, astrocyte IL-6 inhibition required higher concentrations of K+ (greater than or equal to 75 mM). These results demonstrate a novel role for astrocyte potassium channel activity in modulation of glial cytokine production. (C) 2001 Elsevier Science B.V. All rights reserved.