title: Combination of dehydroepiandrosterone and orthovanadate administration reduces intestinal leukocyte recruitment in models of experimental sepsis.
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.
  
  
  RESULTS
  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.affiliation: Department of Anesthesia, Dalhousie University, Halifax, NS, Canada.
authors.forename: Nadia
authors.initials: N
authors.lastname: Al-Banna
authors.affiliation: Department of Anesthesia, Dalhousie University, Halifax, NS, Canada; Department of Anesthesiology and Intensive Care Medicine, Ernst-Moritz-Arndt-Universität, Greifswald, Germany.
authors.forename: Dragan
authors.initials: D
authors.lastname: Pavlovic
authors.affiliation: Department of Anesthesia, Dalhousie University, Halifax, NS, Canada; Department of Anesthesiology and Intensive Care Medicine, Ernst-Moritz-Arndt-Universität, Greifswald, Germany.
authors.forename: Nivin
authors.initials: N
authors.lastname: Sharawi
authors.affiliation: Department of Anesthesia, Dalhousie University, Halifax, NS, Canada; Department of Anesthesiology and Intensive Care Medicine, Ernst-Moritz-Arndt-Universität, Greifswald, Germany.
authors.forename: Vo Hoai
authors.initials: VH
authors.lastname: Bac
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Ernst-Moritz-Arndt-Universität, Greifswald, Germany.
authors.forename: Mathis
authors.initials: M
authors.lastname: Jaskulski
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Ernst-Moritz-Arndt-Universität, Greifswald, Germany.
authors.forename: Claudius
authors.initials: C
authors.lastname: Balzer
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Ernst-Moritz-Arndt-Universität, Greifswald, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Weber
authors.affiliation: Institute for Pathophysiology "Ljubodrag Buba Mihailović", Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Nedeljkov
authors.affiliation: 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.
authors.forename: Christian
authors.initials: C
authors.lastname: Lehmann
mesh_terms: D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D002448:Cell Adhesion / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D016207:Cytokines / Q000097:blood; D003687:Dehydroepiandrosterone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology; D005260:Female; D018836:Inflammation Mediators / Q000097:blood; D007422:Intestines / Q000098:blood supply* / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D010052:Ovariectomy; D051381:Rats; D011917:Rats, Inbred Lew; D018805:Sepsis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D012737:Sex Factors; D013152:Splanchnic Circulation / Q000187:drug effects; D014638:Vanadates / Q000008:administration & dosage*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D014638:Vanadates; D003687:Dehydroepiandrosterone
keywords: Dehydroepiandrosterone (DHEA); Endotoxemia; Intestine; Leukocyte adherence; Microcirculation; Orthovanadate (OV); Sepsis