Recombinant bactericidal/permeability-increasing protein inhibits endotoxin-induced high-mobility group box 1 protein gene expression in sepsis

We investigated in vivo the effect of recombinant bactericidal/permeability-increasing protein (rBPI(21)) on high-mobility group box 1 protein (HMGB1) expression in sepsis and its potential mechanism. Using a sepsis model induced by cecal ligation and puncture (CLIP), rats were randomly divided into four groups as follows: normal control group, sham-operated group, CLP group, and BPI treatment group. Animals were killed at designated time points, and blood and tissue samples from liver, lungs, kidneys, and small intestine were harvested to determine related variables. In addition, we observed the effect of treatment with rBPI(21) on survival rate in septic rats. The results showed that endotoxin content and expression levels of HMGB1 and LIPS binding protein/CD14 mRNA in various organs were significantly increased at 12 and 24 h after CLIP, which can be attenuated by treatment with rBPI(21) (P< 0.05-0.01). Meanwhile, treatment with rBPI(21) in septic rats can markedly reduce serum alanine aminotransferase, creatinine levels, and pulmonary myeloperoxidase activity at 12 and 24 h after CLP, increase diamine oxidase activity at both time points (P < 0.05-0.01), and improve the 1 - to 10-day survival rates in animals subjected to CLP (P = 0.012). These findings suggest that treatment with rBPI(21) can significantly reduce endotoxin contents and expression levels of HMGB1 and LIPS binding protein/CD14 mRNA in various organs in sepsis induced by CLP, and can protect against multiple organ damage resulting from sepsis. The effect of rBP1(21) inhibiting HMGB1 gene expression in sepsis might be associated with endotoxin-dependent mechanisms.