Indomethacin: lack of effect on lethality of endotoxin in rats

The effect of indomethacin on lethality of endotoxin in lead acetate sensitized rats was studied. Rats (334 ± 4 g, n=26) received intravenous injections of endotoxin in lead acetate (5 mg/ml) 0.9% saline. The LD₅₀ of endotoxin was 0.075 mg/kg. Lead acetate caused no mortality at 24 hours. Similar doses of endotoxin in lead acetate were injected intravenously and 12% ethanol (0.6 M phosphate buffer, pH 8.0) administered by gavage to 39 animals. The LD₅₀ was 0.064 mg/kg (not significant). An additional 40 animals received indomethacin (10 mg/kg) in alcohol buffer immediately before injection of endotoxin lead acetate. The LD₅₀ was 0.051 mg/kg (not significant). Indomethacin alone (10 animals) caused no mortality. The dose of indomethacin was sufficient to inhibit prostaglandin synthesis effectively for the 24 hour observation period. Indomethacin does not alter endotoxin caused mortality in lead acetate sensitized rats.