Inhibition of endotoxin-induced interleukin 8 release by teicoplanin in human whole blood.

Abstract

Antibiotic-induced endotoxin (lipopolysaccharide; LPS) release may precipitate septic shock. In the present study the effect of teicoplanin, which has been reported to neutralize LPS in experimental models, on LPS neutralization was investigated in human whole blood samples. Levels of interleukin 8, a preinflammatory cytokine which was stimulated by Salmonella minnesota R595 LPS (12.6 micrograms/ml), were monitored over time. Interleukin 8 concentrations increased over time up to 24 h. When LPS was preincubated with teicoplanin (antibiotic: LPS ratio 20:1, w/w), interleukin 8 concentrations were found significantly (p < 0.05) reduced at 4, 8 and 24 h after LPS challenge. Interleukin 1 beta (at 4, 8 and 24 h) and tumor necrosis factor alpha (at 8 and 24 h) levels were also significantly decreased by teicoplanin. In this experiment model, a teicoplanin:LPS ratio 100-fold less than the ratio achievable in plasma of septic shock patients was able to reduce interleukin 8, which has been correlated with the severity of septic disease.