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.