Background: Endotoxemia usually causes significant morbidity and mortality, and treatment of endotoxemia is often ineffective. The effects of tetrandrine (a bisbenzylisoquinoline alkaloid) on lipopolysaccharide (LPS)-induced endotoxemia were investigated in mice.
Methods: The peritoneal macrophages were stimulated with LPS and treated with or without tetrandrine. The amounts of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-10 secreted by peritoneal macrophages were measured by enzyme-linked immunosorbent assay. Mice were intraperitoneally injected with LPS to induce endotoxemia and were treated or not treated with oral gavage with 150 mg/kg tetrandrine 1 hour before or after LPS injection. The survival rate of the mice was determined after they were treated with various regiments. The amounts of TNF-alpha, IL-1beta, IL-6, and IL-10 in the serum of the mice were measured by enzyme-linked immunosorbent assay, and the high mobility group box 1 (HMGB1) concentration was studied by Western blot analysis.
Results: Tetrandrine suppressed the LPS-induced increase of TNF-alpha, IL-1beta, and HMGB1 secretion by peritoneal macrophages but did not affect the IL-6 and IL-10 concentrations. The animals treated with tetrandrine either 1 hour before or after LPS injection had a 100% survival rate, which was significantly higher than that of the control group (40%) (p = 0.005). The LPS-induced increase in serum TNF-alpha, IL-1beta, and HMGB1 concentrations was reduced by tetrandrine treatment administered either 1 hour before or after LPS injection (p < 0.0001). In contrast, tetrandrine prolonged the LPS-induced elevation in serum IL-10 concentrations only mildly changed the serum IL-6 concentrations.
Conclusions: Tetrandrine treatment either 1 hour before or 1 hour after LPS injection reduced the mortality rate of the mice with LPS-induced endotoxemia. The effects of tetrandrine on LPS-induced endotoxemia might be related to the suppression of TNF-alpha, IL-1beta, and HMGB1 concentrations.