Effects of bactericidal/permeability-increasing protein on endotoxin-induced fever and Escherichia coli-induced shock in rabbits

Binding of bactericidal/permeability-increasing protein (BPI) to endotoxin inhibits endotoxin-triggered responses. We investigated the effects of BPI on endotoxin fever and E. coli-induced septic shock in rabbits. Pre-incubation of endotoxin with BPI blocked fever compared to control rabbits (n = 6). A marked reduction in fever was also observed when BPI was injected before endotoxin. E. coli-challenge resulted in 66% mortality (n = 6); pre-treatment with BPI resulted in survival of all animals (n = 3). Mean arterial blood pressure was higher in BPI-treated compared to control rabbits. Comparable leukopenia and thrombocytopenia was observed with either BPI or vehicle treatment. Tumor necrosis factor (TNF) and interleukin-1 receptor antagonist were similarly elevated in both BPI- and saline-treated rabbits. However, in BPI treated rabbits, peak TNF levels were 34 % lower compared to saline controls (P < 0.05). Further studies are warranted to assess whether BPI may have therapeutic potential for the treatment of septic shock.