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  • Title: Activity of lymphocyte subpopulations in polymicrobial sepsis and DHEA treatment in IL-6 knockout mice.
    Author: Zeckey C, Hildebrand F, Hoevel P, Müller K, Krettek C, Barkhausen T, van Griensven M.
    Journal: J Innate Immun; 2010; 2(5):469-77. PubMed ID: 20375552.
    Abstract:
    INTRODUCTION: Sepsis with subsequent multiorgan dysfunction remains the leading cause of mortality in trauma patients. A gender dimorphism in the host response after trauma and sepsis has been revealed. Dehydroepiandrosterone (DHEA), one of the most abundant adrenal sexual steroid hormones, seems to have a protective immunological effect in sepsis. Knowledge of the pathway is sparse; however, a cellular modulation mediated by interleukin-6 (IL-6) has been proposed. MATERIALS AND METHODS: The effect of DHEA on survival, clinical parameters and the cellular immune system (T lymphocytes and NK cells) was examined in a model of polymicrobial sepsis induced by cecal ligation and puncture. For clarification of the role of IL-6 in the protective effect of DHEA, we used IL-6 knockout mice (IL-6(-/-)). As controls, experiments were performed on wild-type mice (WT). RESULTS: The administration of DHEA in IL-6(-/-) mice did not affect mortality, as it was not significantly different from WT mice without DHEA application. The cellular immune response was influenced, as seen by a significant reduction in the percentage of CD8+ and NK cells in WT animals. CONCLUSIONS: Mortality rates in IL-6(-/-) mouse strains were not lowered by DHEA; therefore, a limited effect of IL-6 on this pathway has to be proposed. NK cells may be one of the effector cells of the protective mechanisms of DHEA, whilst the role of CD8+ lymphocytes remains unclear. Consequently, DHEA might be presented as a possible adjuvant therapy after septic insult for modulation of the dysregulated immune system.
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