Dehydroepiandrosterone modulates survival and immune functions during sepsis depending on the way of drug administration.
BACKGROUND
Administration of dehydroepiandrosterone (DHEA) has been demonstrated to improve survival and cellular immune functions during systemic inflammation. Although there is evidence that the route of drug application may profoundly affect the DHEA-induced effects the impact of this parameter remains to be established.


METHODS
Male NMRI mice were subjected to sham-operation (laparotomy) or sepsis (cecal ligation and puncture). Animals received saline or DHEA (20 mg/kg/day) given either subcutaneously, intravenously, or intraperitoneally. Termination of animals was performed 48 hrs after induction of sepsis in order to monitor splenocyte proliferation ((3)H-thymidine incorporation assay), splenocyte apoptosis (Annexin V binding capacity), and cytokine release (IL-1β and IL-6, ELISA).


RESULTS
Subcutaneous DHEA administration improved the survival rate of septic mice 48 hrs after induction of CLP (75% vs. 47%). This effect was paralleled by a restoration of splenocyte proliferation, a decreased cellular apoptosis rate of splenocytes, and an attenuation of pro-inflammatory cytokine release. In contrast, no significant effects on the survival rate or cellular immune functions were observed following intravenous or intraperitoneal DHEA administration.


CONCLUSIONS
Subcutaneous administration of DHEA induced an increased survival rate and improved cellular immune functions in septic mice. In contrast, no comparable effects were noticed following intravenous or intraperitoneal administration of DHEA.
Schmitz
Daniel
D
Dept. Trauma Surgery, University Hospital of Essen, Essen, Germany.
Kobbe
Philipp
P
Wegner
Alexander
A
Hammes
Florian
F
Oberbeck
Reiner
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology; D015996:Survival Rate
D016207:Cytokines; D003687:Dehydroepiandrosterone