INHIBITION OF ENDOTOXIN-INDUCED INTERLEUKIN-8 RELEASE BY TEICOPLANIN IN HUMAN WHOLE-BLOOD

Antibiotic-induced endotoxin (lipopolysaccharide; LPS) release may pre cipitate 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. Leve ls of interleukin 8, a proinflammatory cytokine which was stimulated b y Salmonella minnesota R595 LPS (12.6 mu g/ml), were monitored over ti me. 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) re duced at 4, 8 and 24 h after LPS challange. Interleukin 1 beta (at 4, 8 and 24 h) and tumor necrosis factor alpha (at 8 and 24 h) levels wer e also significantly decreased by teicoplanin. In this experiment mode l, a teicoplanin: LPS ratio 100-fold less than the ratio achievable in plasma of septic shock patients was able to reduce interleukin 8, whi ch has been correlated with the severity of septic disease.