Related Experiment Videos
Big-endothelin release in baboon bacteremia is partially TNF dependent
1Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria.
The Journal of Laboratory and Clinical Medicine
|December 1, 1994
Summary
Bacteremia increases big-endothelin (big-ET) release, mediated by tumor necrosis factor (TNF). Neutralizing TNF significantly reduced big-ET levels and improved survival in a primate sepsis model.
Area of Science:
- Cardiovascular Physiology
- Immunology
- Endocrinology
Background:
- Big-endothelin (big-ET) is a vasoactive substance crucial for vascular tone regulation.
- The role of big-ET in bacteremia, a serious bloodstream infection, was previously unknown.
- Tumor necrosis factor (TNF) is a key inflammatory mediator implicated in sepsis.
Purpose of the Study:
- To investigate if bacteremia induces big-ET release in a primate model.
- To determine if TNF mediates big-ET release during bacteremia.
- To evaluate the therapeutic potential of anti-TNF antibodies in bacteremia.
Main Methods:
- Infusion of Escherichia coli into male baboons to induce bacteremia.
- Measurement of plasma big-ET and TNF levels using immunoassay.
- Administration of anti-TNF monoclonal antibodies prior to bacterial challenge.
Main Results:
- Bacteremic baboons exhibited significantly elevated plasma big-ET concentrations compared to baseline.
- Anti-TNF antibody treatment attenuated the rise in big-ET and TNF levels.
- Anti-TNF therapy improved hemodynamic stability and reduced mortality from 100% to 0%.
Conclusions:
- TNF plays a critical role in mediating big-ET production/release during bacteremia.
- Neutralization of TNF is a promising therapeutic strategy for improving survival in bacteremia.
- Targeting TNF may mitigate the detrimental effects of big-ET in sepsis.