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An exaggerated inflammatory response after CLP correlates with a negative outcome
Manuel B Torres1, Antonio De Maio
1Division of Pediatric Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
The Journal of Surgical Research
|April 20, 2005
Summary
Sepsis outcomes in mice depend on the severity of the initial injury and the animal's genetic background. Different genetic make-ups and insult severities significantly alter mortality rates and cytokine profiles in experimental sepsis.
Area of Science:
- Immunology
- Sepsis Pathophysiology
- Genetics
Background:
- Sepsis is a major cause of death in surgical intensive care units.
- Patient outcomes in sepsis vary due to factors like the initial insult, environment, and host genetics.
- This study investigates how insult severity and genetic background influence sepsis progression.
Purpose of the Study:
- To investigate the impact of varying insult severity and genetic background on sepsis outcomes.
- To analyze the resulting cytokine profiles and mortality rates in a murine model.
Main Methods:
- Male A/J and C57BL/6J (B6) mice underwent cecal ligation and puncture (CLP) with varying ligation lengths and needle gauges.
- Plasma cytokine levels (TNF-alpha, IL-6, IL-10) were measured using ELISA at different time points post-CLP.
- Mortality rates were recorded and compared between groups.
Main Results:
- A/J mice showed higher TNF-alpha and IL-6 levels than B6 mice after CLP16 (1-cm ligation).
- More severe insults (>1-cm ligation) led to increased cytokine expression compared to less severe insults.
- Higher mortality was observed in B6 mice with a >1-cm ligation compared to 1-cm ligation.
Conclusions:
- Mortality rates and cytokine profiles in sepsis are significantly influenced by both the severity of the initiating insult and the host's genetic makeup.
- These findings highlight the complex interplay between external factors and host genetics in determining sepsis outcomes.