OBJECTIVE: To investigate the effect of bactericidal/permeability-increasing protein(BPI) on the outcome of sepsis in mice and its possible mechanism. METHODS: Sepsis was induced by injection of 2x10(6) colony-formed unit E. coli J5 via the tail vein. BPI of 5 mg/kg or equal volume of normal saline(NS) were injected intravenously at the same time. Endotoxin and TNFalpha levels in serum were assayed using a chromogenic limulus amebocyte lysate test and ELISA respectively. RESULTS: Seventy-two hour survival rate of septic mice was significantly higher in the BPI group (15/18) than in the NS group(8/18, P<0.01). Serum endotoxin levels in the BPI group (1.3+/-0.3 and 0.7+/-0.4 &mgr;g/L) were significantly lower than those in the NS group (3.9+/-0.8 and 2.5+/-0.9 &mgr; g/L, P<0.01) 0.5 and 1 hour following injection of bacteria respectively. The peak levels of serum tumor necrosis factor-alpha(TNFalpha)in the BPI group (1.9+/-0.6 &mgr;g/L) were also markedly lower than those in the NS group (3.8+/-0.8 &mgr;g/L, P<0.01) 1.5 hours following bacterial injection. But there was no significant difference in blood bacterial count between the BPI and NS groups 0.5, 1.5 and 3.0 hours after injection of bacteria. CONCLUSIONS: BPI has a marked protective effect on E. coli sepsis, which might be related to its action against bacterial endotoxin and its inhibition of TNFalpha production in sepsis.
OBJECTIVE: To investigate the effect of bactericidal/permeability-increasing protein(BPI) on the outcome of sepsis in mice and its possible mechanism. METHODS:Sepsis was induced by injection of 2x10(6) colony-formed unit E. coli J5 via the tail vein. BPI of 5 mg/kg or equal volume of normal saline(NS) were injected intravenously at the same time. Endotoxin and TNFalpha levels in serum were assayed using a chromogenic limulus amebocyte lysate test and ELISA respectively. RESULTS: Seventy-two hour survival rate of septic mice was significantly higher in the BPI group (15/18) than in the NS group(8/18, P<0.01). Serum endotoxin levels in the BPI group (1.3+/-0.3 and 0.7+/-0.4 &mgr;g/L) were significantly lower than those in the NS group (3.9+/-0.8 and 2.5+/-0.9 &mgr; g/L, P<0.01) 0.5 and 1 hour following injection of bacteria respectively. The peak levels of serum tumor necrosis factor-alpha(TNFalpha)in the BPI group (1.9+/-0.6 &mgr;g/L) were also markedly lower than those in the NS group (3.8+/-0.8 &mgr;g/L, P<0.01) 1.5 hours following bacterial injection. But there was no significant difference in blood bacterial count between the BPI and NS groups 0.5, 1.5 and 3.0 hours after injection of bacteria. CONCLUSIONS:BPI has a marked protective effect on E. coli sepsis, which might be related to its action against bacterial endotoxin and its inhibition of TNFalpha production in sepsis.
Authors: Dawn M E Bowdish; Donald J Davidson; Monisha G Scott; Robert E W Hancock Journal: Antimicrob Agents Chemother Date: 2005-05 Impact factor: 5.191