| Abstract | BACKGROUND: Traumatic shock activates the hypothalamic-pituitary-adrenal axis (HPA) to mediate a cascade of defensive mechanisms that often include overwhelming inflammatory response and immunosuppression, which may lead to multiple organ failure. Androstenetriol (5 androstene, 3beta, 7beta, 17beta triol-AET) is a metabolite of dehydroepiandrosterone that markedly up regulates host immune response, prevents immune suppression, modulates inflammation and improves survival after lethal infections by pathogens and lethal radiation. HYPOTHESIS: AET-induced immune modulation will improve survival in a conscious rodent model of traumatic shock. METHODS: A relevant traumatic shock rodent model that applies to both combat and civilian sectors was used. After creation of a midline laparotomy (soft tissue trauma), animals were hemorrhaged to a mean arterial pressure of 35-40 mm Hg. Resuscitation was initiated sixty minutes later with crystalloid fluid and packed red blood cells and animals were observed for two days. In a randomized and blinded fashion, AET or vehicle was administered subcutaneously at the beginning of resuscitation. RESULTS: In the vehicle group 5 out of 16 animals survived, (31%). In contrast, 9 out of 13 animals who received AET survived (69%), (Fisher Exact Test p < 0.05). Survival in the AET treatment group was associated with reduced levels of IL-6, IL-10, and IL-18, and enhanced IFN-gamma and IL-2 levels. CONCLUSION:: The results indicate that AET provides a significant protective effect and improves survival in a clinically relevant model of traumatic hemorrhagic shock. AET protective effects are associated with an elevation of Th1 and reduction of Th2 cytokines. |
| Authors | Andreea C Marcu, Kristin E Paccione, R Wayne Barbee, Robert F Diegelmann, Rao R Ivatury, Kevin R Ward, Roger M Loria
(Affiliation: Virginia Commonwealth University Reanimation Engineering Shock Center (VCURES), Virginia Commonwealth University, Richmond, Virginia, USA.)
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| Journal | The Journal of trauma
(J Trauma)
Vol. 63
Issue 3
Pg. 662-9
(Sep 2007)
ISSN: 1529-8809 United States |
| PMID | 18073617
(Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
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| Chemical References |
- 5-androstene-3,7,17-triol
- Androstenols
- Immunologic Factors
- Interleukin-6
- Interleukin-8
- Interleukin-10
|
| Topics |
- Androstenols
(pharmacology)
- Animals
- Disease Models, Animal
- Immunologic Factors
(pharmacology)
- Interleukin-10
(blood)
- Interleukin-6
(blood)
- Interleukin-8
(blood)
- Male
- Random Allocation
- Rats
- Rats, Sprague-Dawley
- Resuscitation
- Shock, Traumatic
(drug therapy, physiopathology)
|
