Time-dependent effect of LPS on PGE₂ and TNF-α production by rat glial brain culture: Influence of COX and cytokine inhibitors

This study was undertaken to investigate the effect of lipopolysaccharide (LPS) stimulation on the time course of prostaglandin E₂ (PGE₂) and tumor necrosis factor alpha (TNF-α) production by rat glial brain culture. A concentration of 10 μg/ml LPS from Escherichia coli was used as stimulation treatment. The effect of pentoxifylline (PXF), nimesulide (NIM), indomethacin (INDO) and dexamethasone (DEX) on the regulation of PGE₂ and TNF-α production was tested. Stimulation of rat glial cells with LPS resulted in different time-dependent production patterns of PGE₂ and TNF-α. The time course of TNF-α elevation was short, reaching its peak at 6 h post LPS and decreasing to undetectable levels after 24 h. On the other hand, the time course of PGE₂ elevation was longer, starting at 6 h post LPS treatment and increasing 100-fold compared with basal levels, 24 h post LPS exposure. The COX inhibitors (NIM and INDO) and DEX were found to inhibit the LPS-induced elevation in PGE₂ production, while PXF lacked such an inhibitory effect. Furthermore, NIM, DEX and PXF were found to reduce the LPS-induced elevation in TNF-α levels, while INDO caused a greater elevation in TNF-α levels. These results may cast further light on the LPS-induced production of PGE₂ and TNF-α by rat glial cell cultures and the relation between the two systems.