Bacterial lipopolysaccharide increases interleukin-6 and prostaglandin release in rat cortical type I astrocytes by different mechanisms: Role of anti-inflammatory agents

LPS stimulated IL-6 release in a concentration-dependent manner from rat cortical type I astrocytes. This stimulatory action was completely abolished by Dexamethasone (DEX), but was not affected by indomethacin (IND), a 5-cyclooxigenase inhibitor. LPS-induced IL-6 release was partially inhibited by BW 4AC, a 5-lipoxygenase inhibitor. LPS concentration-dependently increased the release of PGE(2) from type I astrocytes, an effect completely inhibited by IND. To rule out the possibility that DEX was inhibiting LPS-induced IL-6 release by blocking IL-6 gene expression, we tested the effect of DEX on interleukin 1 beta(IL-1)induced IL-6 release. DEX slightly inhibited IL-1-induced IL-6 release, while IL-1 releasing action on IL-6 was significantly reduced by IND. The involvement of nitric oxide (NO) generation on LPS-induced IL-6 release was also studied. We found that L-NO-arginine, an inhibitor of nitric oxide synthase, concentration-dependently reduced LPS-induced IL-6 release in astrocytes. In conclusion, we provide evidence that LPS action on IL-6 and PGE(2) release can be ascribed to the activation of different transduction mechanisms, which can be pharmacologically dissected with the aid of anti-inflammatory drugs. (C) 1998 Academic Press.