Activity of lymphocyte subpopulations in polymicrobial sepsis and DHEA treatment in IL-6 knockout mice

Christian Zeckey, Frank Hildebrand, Petra Hoevel, Kathrin Müller, Christian Krettek, Tanja Barkhausen, Martijn Van Griensven

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


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.

Original languageEnglish
Pages (from-to)469-477
Number of pages9
JournalJournal of Innate Immunity
Issue number5
StatePublished - Aug 2010
Externally publishedYes


  • CD8 cells
  • Dehydroepiandrosterone
  • Immunomodulation
  • Interleukin 6
  • Lymphocyte subpopulations
  • Natural killer cells
  • Sepsis
  • Shock


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