We investigated inflammatory and physiologic parameters in
sepsis models of increasing lethality induced by cecal
ligation and
puncture (CLP). Mice received
imipenem for
antibiotic therapy, and groups were sacrificed at 2, 4, 8, 12, 16, 20, and 24 h after CLP. The severity of
sepsis increased with needle
puncture size (lethality with 18-gauge
puncture [18G], 100%; 21G, 50%; 25G, 5%;
sham treatment, 0%). While the temperature (at 12 h) and the activity and diurnal rhythm (at day 4) of the 25G-treated CLP group recovered to normal, the 21G and 18G treatment groups exhibited severe
hypothermia along with decreased activities. A direct correlation was also observed between the severity of
sepsis and
cytokine (
interleukin 1beta [IL-1beta],
tumor necrosis factor [TNF], IL-6, and IL-10) concentrations in both the peritoneum and the plasma. There were substantially higher
cytokine levels in the more severe CLP models than in the
sham-treated one. Peritoneal and plasma TNF levels were always less than 40 pg/ml in all models. None of the
cytokines in the septic mice peaked within the first hour, which is in contrast to the results of most
endotoxin models.
Chemokine (KC and
macrophage inflammatory protein 2) profiles also correlated with the severity of
sepsis. Except for the
chemokines, levels of inflammatory mediators were always higher at the site of
inflammation (peritoneum) than in the circulation. Our study demonstrated that
sepsis of increasing severity induced increased
cytokine levels both within the local environment (peritoneum) and systemically (plasma), which in turn correlated with morbidity and mortality.