Inhibition of astrocyte TNF alpha expression by extracellular potassium

TNF alpha and IL-6 are cytokines of great interest, given the numerous biol ogical 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 m echanisms of cytokine regulation in the inflamed CNS. Since one of the majo r functions of astrocytes is spatial buffering of K+ ions, we examined the effect of high extracellular KCl on astrocyte cytokine expression by ribonu clease protection assay and ELISA. Results demonstrate that astrocyte TNF a lpha production was potently inhibited by K+ with 44 and 89% inhibition at 25 and 55 mM K+, respectively. In contrast, astrocyte IL-6 inhibition requi red higher concentrations of K+ (greater than or equal to 75 mM). These res ults demonstrate a novel role for astrocyte potassium channel activity in m odulation of glial cytokine production. (C) 2001 Elsevier Science B.V. All rights reserved.