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


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.
Zeckey
Christian
C
Trauma Department, Hannover Medical School, Hannover, Germany.
Hildebrand
Frank
F
Hoevel
Petra
P
Müller
Kathrin
K
Krettek
Christian
C
Barkhausen
Tanja
T
van Griensven
Martijn
M
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003687:Dehydroepiandrosterone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D007694:Killer Cells, Natural / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology / Q000401:mortality*; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D015850:Interleukin-6; D003687:Dehydroepiandrosterone