Dehydroepiandrosterone decreases mortality rate and improves cellular immune function during polymicrobial sepsis.
OBJECTIVE
Sepsis is associated with a marked depression of cellular immune function. The steroid hormone dehydroepiandrosterone (DHEA) is proposed to have immunoenhancing activities. We, therefore, investigated the effect of DHEA on the mortality rate and cellular immune functions in an experimental model of sepsis.


METHODS
Randomized animal study.


METHODS
Level I trauma center, university research laboratory.


METHODS
Male NMRI mice.


METHODS
Mice were subjected to laparotomy (sham) or cecal ligation and puncture (CLP). Mice were treated with (sham/DHEA; CLP/DHEA) or without (sham; CLP) the steroid hormone DHEA (30 mg/kg sc). Animals were killed 48 hrs after the onset of sepsis.


RESULTS
The survival rate of septic mice was determined 24 and 48 hrs after onset of sepsis. Forty-eight hours after the septic challenge, a white blood cell count was performed and serum tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta concentrations were monitored using ELISA. Furthermore, the delayed type of hypersensitivity (DTH) reaction was evaluated on the basis of ear pinna swelling after dinitrofluorobenzene (DNFB) administration, and clinical variables (body weight, temperature, heart rate, fluid input/output, food intake) were monitored using metabolic cages. DHEA administration improved the survival rate (87% vs. 53% after 48 hrs; p <.001). This was accompanied by a restoration of the depressed DTH reaction and a reduction in TNF-alpha serum concentrations (20.7 +/- 1.4 pg/mL vs. 32.4 +/- 6.6 pg/mL).


CONCLUSIONS
These results demonstrate that DHEA administration leads to an increased survival following a septic challenge. The immunoenhancing effect of DHEA is accompanied by a reduction of TNF-alpha release and an improved activity of T-cellular immunity. DHEA administration may, therefore, be beneficial in systemic inflammation.
Department of Trauma Surgery, University Hospital of Essen, Essen, Germany.
R
R
Oberbeck
M
M
Dahlweid
R
R
Koch
M
M
van Griensven
A
A
Emmendörfer
H
H
Tscherne
H C
HC
Pape
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D001424:Bacterial Infections / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D003687:Dehydroepiandrosterone / Q000276:immunology* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004797:Enzyme-Linked Immunosorbent Assay; D007111:Immunity, Cellular / Q000187:drug effects* / Q000276:immunology; D007375:Interleukin-1 / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011897:Random Allocation; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D000276:Adjuvants, Immunologic; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D003687:Dehydroepiandrosterone