Journal article
Immunopathologic Alterations in Murine Models of Sepsis of Increasing Severity
Infection and immunity, Vol.67(12), pp.6603-6610
12/1999
Handle:
https://hdl.handle.net/2376/106206
PMCID: PMC97073
PMID: 10569781
Abstract
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 1β [IL-1β],
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.
Metrics
4 Record Views
Details
- Title
- Immunopathologic Alterations in Murine Models of Sepsis of Increasing Severity
- Creators
- Samuel Ebong - Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0602Douglas Call - Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0602Jean Nemzek - Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0602Gerald Bolgos - Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0602David Newcomb - Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0602Daniel Remick - Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0602
- Publication Details
- Infection and immunity, Vol.67(12), pp.6603-6610
- Academic Unit
- Paul G. Allen School for Global Animal Health
- Publisher
- American Society for Microbiology (ASM)
- Identifiers
- 99900546805901842
- Language
- English
- Resource Type
- Journal article