title: Platelet-activating factor or a platelet-activating factor antagonist decreases tumor necrosis factor-alpha in the plasma of mice treated with endotoxin.
abstract: 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 (TNF alpha) 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 TNF alpha levels in LPS-treated mice. The decrease in plasma TNF alpha induced by L-PAF or alprazolam was partly reversed by indomethacin. Despite a decrease in plasma TNF alpha, L-PAF or alprazolam caused an increase in the amount of TNF alpha mRNA present in the kidneys and the livers of LPS-treated mice, suggesting that a posttranscriptional event leading to the synthesis or release of TNF alpha was inhibited by these agents.
authors.affiliation: Medical Research Division, American Cyanamid Company, Lederle Laboratories, Pearl River, NY 10965.
authors.forename: K M
authors.initials: KM
authors.lastname: Ferguson-Chanowitz
authors.forename: A S
authors.initials: AS
authors.lastname: Katocs
authors.forename: W C
authors.initials: WC
authors.lastname: Pickett
authors.forename: J B
authors.initials: JB
authors.lastname: Kaplan
authors.forename: P M
authors.initials: PM
authors.lastname: Sass
authors.forename: A L
authors.initials: AL
authors.lastname: Oronsky
authors.forename: S S
authors.initials: SS
authors.lastname: Kerwar
mesh_terms: D000525:Alprazolam / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D004731:Endotoxins / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000737:chemistry; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D010972:Platelet Activating Factor / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D012772:Shock, Septic / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007213:Indomethacin; D000525:Alprazolam