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Prevention of Hypovolemic Circulatory Collapse by IL-6 Activated Stat3
- Source :
- PLoS ONE, Vol 3, Iss 2, p e1605 (2008), PLoS ONE
- Publication Year :
- 2008
-
Abstract
- Half of trauma deaths are attributable to hypovolemic circulatory collapse (HCC). We established a model of HCC in rats involving minor trauma plus severe hemorrhagic shock (HS). HCC in this model was accompanied by a 50% reduction in peak acceleration of aortic blood flow and cardiomyocyte apoptosis. HCC and apoptosis increased with increasing duration of hypotension. Apoptosis required resuscitation, which provided an opportunity to intervene therapeutically. Administration of IL-6 completely reversed HCC, prevented cardiac dysfunction and cardiomyocyte apoptosis, reduced mortality 5-fold and activated intracardiac signal transducer and activator of transcription (STAT) 3. Pre-treatment of rats with a selective inhibitor of Stat3, T40214, reduced the IL-6-mediated increase in cardiac Stat3 activity, blocked successful resuscitation by IL-6 and reversed IL-6-mediated protection from cardiac apoptosis. The hearts of mice deficient in the naturally occurring dominant negative isoform of Stat3, Stat3beta, were completely resistant to HS-induced apoptosis. Microarray analysis of hearts focusing on apoptosis related genes revealed that expression of 29% of apoptosis related genes was altered in HS vs. sham rats. IL-6 treatment normalized the expression of these genes, while T40214 pretreatment prevented IL-6-mediated normalization. Thus, cardiac dysfunction, cardiomyocyte apoptosis and induction of apoptosis pathway genes are important components of HCC; IL-6 administration prevented HCC by blocking cardiomyocyte apoptosis and induction of apoptosis pathway genes via Stat3 and warrants further study as a resuscitation adjuvant for prevention of HCC and death in trauma patients.
- Subjects :
- STAT3 Transcription Factor
Resuscitation
Circulatory collapse
Cardiovascular Disorders
Hypovolemia
lcsh:Medicine
Apoptosis
Biology
Trauma
hypovolemic circulatory collapse
IL-6
Stat3
medicine
Animals
Myocytes, Cardiac
STAT3
Interleukin 6
lcsh:Science
Critical Care and Emergency Medicine/Trauma
Multidisciplinary
Interleukin-6
Physiology/Cardiovascular Physiology and Circulation
lcsh:R
Shock
medicine.disease
Rats
Disease Models, Animal
Shock (circulatory)
Immunology
STAT protein
biology.protein
Cancer research
lcsh:Q
medicine.symptom
Signal transduction
Signal Transduction
Research Article
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- PLoS ONE, Vol 3, Iss 2, p e1605 (2008), PLoS ONE
- Accession number :
- edsair.doi.dedup.....8c322b6699f55e1e176ef9dbb6692fb8