Plasma acid phosphatase levels in endotoxaemia: modification by drugs and chemically detoxified endotoxins

Abstract

The ability of chemically detoxified E. coli endotoxins and membrane-active agents to modify the toxicity of native E. coli endotoxin in vivo was examined. The time- and dose-dependent increase in plasma acid phosphatase activity following toxin administration to rats provided a convenient quantitative measure of in vivo toxicity under various experimental conditions. Treatment of endotoxin with either sodium hydroxide or sodium periodate produced substances which, when injected alone, failed to cause an increase in plasma acid phosphatase activity. When given before native endotoxin, periodate-detoxified toxin produced a dose-dependent reduction in the elevation of plasma enzyme activity caused by unmodified toxin. Pretreatment with pranolium, hydrocortisone or (+)-propranolol also reduced the in vivo toxicity of endotoxin. Mortality studies in mice provided further independent support for the effectiveness of periodate-detoxified endotoxin and membrane-active drugs as endotoxin antagonists. Evidence has been found that under certain conditions gentamicin may act synergistically with bacterial endotoxins in vivo.