Septic shock induced by microbial products and indomethacin

Lethal toxicity was induced in mice by sequential administration of β‐glucan and indomethacin. Whole cell preparations of Gram‐positive bacteria, Gram‐negative bacteria, and fungi also showed a similar toxicity. However, bacterial lipopolysaccharides (LPS) alone were not toxic. After the indomethacin administration, the sensitivity of mice to LPS was significantly elevated and the animals died following only a 0.1‐μg intravenous administration. An accumulation of leukocytes in the liver and enhancement of TNF, IL‐6, and MIP‐2 concentrations were noted. Antibiotic treatment prolonged the survival of mice. The toxicity resembles septic shock, and is strongly related to microbial translocation and endotoxin absorption from the gut. Drug Dev. Res. 55:139–148, 2002.