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 (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.
Ferguson-Chanowitz
K M
KM
Medical Research Division, American Cyanamid Company, Lederle Laboratories, Pearl River, NY 10965.
Katocs
A S
AS
Pickett
W C
WC
Kaplan
J B
JB
Sass
P M
PM
Oronsky
A L
AL
Kerwar
S S
SS
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*
D004731:Endotoxins; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007213:Indomethacin; D000525:Alprazolam