Androstenetriol immunomodulation improves survival in a severe trauma hemorrhage shock model.

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
• Journal: The Journal of trauma (J Trauma) Vol. 63 Issue 3 Pg. 662-9 (Sep 2007) ISSN: 1529-8809 [Electronic] United States
• PMID: 18073617 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

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)