Nadia Al-Banna1, Dragan Pavlovic2, Nivin Sharawi2, Vo Hoai Bac2, Mathis Jaskulski3, Claudius Balzer3, Stefan Weber3, Vladimir Nedeljkov4, Christian Lehmann5. 1. Department of Anesthesia, Dalhousie University, Halifax, NS, Canada. 2. Department of Anesthesia, Dalhousie University, Halifax, NS, Canada; Department of Anesthesiology and Intensive Care Medicine, Ernst-Moritz-Arndt-Universität, Greifswald, Germany. 3. Department of Anesthesiology and Intensive Care Medicine, Ernst-Moritz-Arndt-Universität, Greifswald, Germany. 4. Institute for Pathophysiology "Ljubodrag Buba Mihailović", Faculty of Medicine, University of Belgrade, Belgrade, Serbia. 5. Department of Anesthesia, Dalhousie University, Halifax, NS, Canada; Department of Anesthesiology and Intensive Care Medicine, Ernst-Moritz-Arndt-Universität, Greifswald, Germany. Electronic address: chlehmann@dal.ca.
Abstract
BACKGROUND: Dehydroepiandrosterone (DHEA) was shown to improve the immune function and survival in experimental sepsis. This study examined the effect of DHEA on intestinal leukocyte recruitment during experimental sepsis, considering factors of gender (male, female and ovariectomized female animals) and combined treatment using orthovanadate (OV) in two models of sepsis. METHODOLOGY/ FINDINGS: Male rats underwent colon ascendens stent peritonitis (CASP) or endotoxemia. DHEA was administered after induction of experimental sepsis. Changes in leukocyte adherence and capillary perfusion (measured as intestinal functional capillary density - FCD) were assessed using intravital microscopy. While DHEA increased baseline leukocyte adherence in control animals, DHEA reduced leukocyte adherence and increased FCD in male animals with CASP. These effects were also observed in DHEA-treated ovariectomized female rats with CASP. Similarly, the administration of DHEA reduced the number of adherent leukocytes to intestinal venules by 30% in the endotoxemia model. The combined treatment of DHEA and OV significantly reduced adherence of leukocytes to intestinal venules and improved FCD. CONCLUSIONS: Our results indicate that DHEA is able to reduce intestinal leukocyte recruitment induced by experimental sepsis. Combination of DHEA with OV inhibits leukocyte adherence to intestinal endothelium, similar to what is achieved by the single administration of DHEA but with significantly improved FCD. These findings suggest a potential role for DHEA and OV in clinical sepsis.
BACKGROUND:Dehydroepiandrosterone (DHEA) was shown to improve the immune function and survival in experimental sepsis. This study examined the effect of DHEA on intestinal leukocyte recruitment during experimental sepsis, considering factors of gender (male, female and ovariectomized female animals) and combined treatment using orthovanadate (OV) in two models of sepsis. METHODOLOGY/ FINDINGS: Male rats underwent colon ascendens stent peritonitis (CASP) or endotoxemia. DHEA was administered after induction of experimental sepsis. Changes in leukocyte adherence and capillary perfusion (measured as intestinal functional capillary density - FCD) were assessed using intravital microscopy. While DHEA increased baseline leukocyte adherence in control animals, DHEA reduced leukocyte adherence and increased FCD in male animals with CASP. These effects were also observed in DHEA-treated ovariectomized female rats with CASP. Similarly, the administration of DHEA reduced the number of adherent leukocytes to intestinal venules by 30% in the endotoxemia model. The combined treatment of DHEA and OV significantly reduced adherence of leukocytes to intestinal venules and improved FCD. CONCLUSIONS: Our results indicate that DHEA is able to reduce intestinal leukocyte recruitment induced by experimental sepsis. Combination of DHEA with OV inhibits leukocyte adherence to intestinal endothelium, similar to what is achieved by the single administration of DHEA but with significantly improved FCD. These findings suggest a potential role for DHEA and OV in clinical sepsis.
Authors: Alexander C Paulus; Kathrin Ebinger; Xiangyun Cheng; Sandra Haßelt; Patrick Weber; J Philippe Kretzer; Rainer Bader; Sandra Utzschneider Journal: Biomed Res Int Date: 2019-10-29 Impact factor: 3.411