PLATELET-ACTIVATING-FACTOR OR A PLATELET-ACTIVATING-FACTOR ANTAGONIST DECREASES TUMOR-NECROSIS-FACTOR-ALPHA IN THE PLASMA OF MICE TREATED WITH ENDOTOXIN

When L-platelet-activating factor (PAF) or alprazolam (a PAF antagonist) was administered to lipopolysaccharide (LPS)-treated mice, the level of plasma tumor necrosis factor (TNFα) determined by either ELISA or a cytotoxic assay using WEHI cells was significantly lowered. The inactive stereoisomer, D-PAF, was not effective in lowering plasma TNFα levels in LPS-treated mice. The decrease in plasma TNFα induced by L-PAF or alprazolam was partly reversed by indomethacin. Despite a decrease in plasma TNFα, L-PAF or alprazolam caused an increase in the amount of TNFα mRNA present in the kidneys and the livers of LPS-treated mice, suggesting that a posttranscriptional event leading to the synthesis or release of TNFα was inhibited by these agents. © 1990, by The University of Chicago.