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Updated: Jun 25, 2026
07:34
Use of Animal Model of Sepsis to Evaluate Novel Herbal Therapies
Published on: April 11, 2012
Central sympatholytics prolong survival in experimental sepsis
Stefan Hofer1, Jochen Steppan, Tanja Wagner
1Department of Anaesthesiology, University Hospital Heidelberg, Heidelberg, Germany. Stefan.Hofer@med.uni-heidelberg.de
Critical Care (London, England)
|February 7, 2009
Summary
Pre-emptive administration of clonidine, a central alpha-2 agonist, significantly improved survival in experimental sepsis by reducing pro-inflammatory cytokines and inhibiting sympathetic tone. Postoperative administration did not show significant survival benefits.
Area of Science:
- Critical Care Medicine
- Pharmacology
- Immunology
Background:
- Sepsis is a leading cause of death in intensive care units, characterized by pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6) and NF-kappaB upregulation.
- Clonidine, a central alpha-2 agonist, has previously demonstrated the ability to reduce pro-inflammatory cytokines in surgical patients.
Purpose of the Study:
- To investigate the therapeutic potential of clonidine in improving survival in experimental sepsis.
- To determine if clonidine inhibits sympathetic tone and consequently reduces pro-inflammatory cytokine release.
Main Methods:
- A murine model of caecal ligation and puncture (CLP) induced sepsis was used.
- Animals received pre-emptive or postoperative injections of clonidine (5 microg/kg) or dexmedetomidine (40 microg/kg).
- Control groups received solvent injections; cytokine response and NF-kappaB activity were measured.
Main Results:
- Pre-emptive administration of clonidine and dexmedetomidine significantly reduced mortality in experimental sepsis.
- Pre-emptive clonidine attenuated cytokine response (IL-1beta, IL-6, TNF-alpha), preserved blood pressure, and down-regulated NF-kappaB activity.
- Postoperative clonidine administration did not significantly prolong survival.
Conclusions:
- Pre-emptive administration of clonidine or dexmedetomidine improves survival in experimental sepsis.
- Sympatholytics may serve as adjunct sedatives for sepsis patients by down-regulating pro-inflammatory mediators.
- A connection exists between the central muscarinic network and vagal cholinergic response in sepsis management.
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