Pretreatment with anti-flagellin serum delays acute lung injury in rats with sepsis

摘要

Objective: This study examined the reduction of sepsis-induced ALI by inhibition of flagellin-stimulated TLR5 signaling. Methods: Rats were randomly divided into three groups: one group served as the sham-operated group (control group), and the other two groups received the induction of sepsis (sepsis and treatment groups). The treatment group was injected with anti-flagellin serum before induction of sepsis. At 2, 4, 6, 12, 24, and 48 h following induction of sepsis (six time-point subgroups, n = 10 per subgroup), arterial PaO 2, wet/dry (W/D) lung weight ratios, levels of serum and BALF flagellin and TNF-α, pulmonary pathological alterations, and TLR5 mRNA expression in the lungs were examined. Results: Compared to sham-operated rats, septic rats had: increased levels of serum and BALF flagellin at 6, 12, 24, and 48 h; reduced arterial PaO 2; elevated W/D lung weight ratio; increased serum and BALF TNF-α levels; and upregulated TLR5 mRNA expression at 12, 24, and 48 h (P0.01). Pretreatment with anti-flagellin serum, however, significantly inhibited sepsis-associated declines in arterial PaO 2, increased W/D lung weight ratios, elevated serum and BALF TNF-α levels, and up-regulated TLR5 mRNA expression at 24 and 48 h (P0.01). Conclusion: Neutralizing the actions of circulating flagellin with anti-flagellin serum delayed the development of ALI in rats with sepsis.