Role of nitric oxide in the failure of neutrophil migration in sepsis

The cecal ligation and puncture (CLP) model was used to investigate whether failure of neutrophil migration occurs in sepsis and whether it correlates with disease outcome. It was observed that the severity of sepsis correlat es with the number of punctures in the cecum: mice with 2 punctures (sublet hal [SL]-CLP) developed mild peritonitis (100% survived), whereas mice with 12 punctures (lethal [L]-CLP) developed severe peritonitis and bacteremia that evolved to sepsis (none survived). The production of tumor necrosis fa ctor-alpha, interleukin-1 beta and interleukin-10 was higher in L-CLP than in SL-CLP mice. The impairment of neutrophil migration to the peritoneum an d to the cecum wall was observed only in L-CLP mice. This phenomenon was sh own to be mediated by nitric oxide, because aminoguanidine prevented the fa ilure of neutrophil migration and improved the survival of L-CLP animals. I n conclusion, impairment of neutrophil migration is a crucial event in the worsening of sepsis, and nitric oxide seems to be responsible for the pheno menon.