Dehydroepiandrosterone Modulates Survival and Immune Functions During Sepsis Depending on the Way of Drug Administration

Author(s): Daniel Schmitz, Philipp Kobbe, Alexander Wegner, Florian Hammes, Reiner Oberbeck.

Journal Name: Medicinal Chemistry

Volume 6 , Issue 4 , 2010

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Abstract:

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. Materials and 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 (3H-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.

Keywords: DHEA, drug administration, immune system, mouse, sepsis, survival, Dehydroepiandrosterone, systemic inflammation, laparotomy, 3H-thymidine incorporation assay, splenocyte apoptosis, Annexin V binding capacity, cytokine release, IL-1, IL-6, ELISA, apoptosis, cecal ligation and puncture, Polymicrobial Sepsis Model, ice-cooled RPMI Medium, 96-well microtiter plate, FITC-conjugated recombinant An-nexin V, flow cytome-try, Kaplan-Meier and Cox regression test, Splenocye proliferation, LAP DHEA, CLP DHEA, sham-operated groups, murine models of sepsis

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Article Details

VOLUME: 6
ISSUE: 4
Year: 2010
Page: [229 - 232]
Pages: 4
DOI: 10.2174/1573406411006040229
Price: $58

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