Androstenetriol Immunomodulation Improves Survival in a Severe Trauma Hemorrhage Shock Model
| Autor: | Rao R. Ivatury, Kristin E. Paccione, Andreea C. Marcu, Kevin R. Ward, R. Wayne Barbee, Robert F. Diegelmann, Roger M. Loria |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Resuscitation Mean arterial pressure medicine.medical_treatment Inflammation Critical Care and Intensive Care Medicine Rats Sprague-Dawley Random Allocation Immune system medicine Animals Immunologic Factors Shock Traumatic Androstenols Interleukin-6 business.industry Interleukin-8 Immunosuppression Interleukin-10 Rats Traumatic Shock Disease Models Animal Anesthesia Shock (circulatory) Immunology Surgery medicine.symptom business Packed red blood cells |
| Zdroj: | Journal of Trauma: Injury, Infection & Critical Care. 63:662-669 |
| ISSN: | 0022-5282 |
| Popis: | 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, 3 ,7 ,1 7 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, IL10, and IL-18, and enhanced IFN- 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. |
| Databáze: | OpenAIRE |
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