title: Effect of extracorporeal cytokine removal on vascular barrier function in a septic shock patient.
abstract: BACKGROUND
  Sepsis and septic shock are major healthcare problems, affecting millions of individuals around the world each year. Pathophysiologically, septic multiple organ dysfunction (MOD) is a life-threatening condition caused by an overwhelming systemic inflammatory response of the host's organism to an infection. We experimentally tested if high circulating cytokine levels might increase vascular permeability-a critical hallmark of the disease-and if this phenomenon can be reversed by therapeutic cytokine removal (CytoSorb®) in an exemplary patient.
  
  
  METHODS
  A 32-year-old Caucasian female presented with septic shock and accompanying acute kidney injury (Sequential Organ Failure Assessment (SOFA) = 18) to our ICU. In spite of a broad anti-infective regimen, adequate fluid resuscitation, and high doses of inotropics and catecholamines, she remained refractory hypotensive. The extraordinary severity of septic shock suggested an immense overwhelming host response assumingly accompanied by a notable cytokine storm such as known from patients with toxic shock syndrome. Thus, a CytoSorb® filter was added to the dialysis circuit to remove excess shock-perpetuating cytokines. To analyze the endothelial phenotype in vitro before and after extracorporeal cytokine removal, we tested the septic shock patient's serum on human umbilical vein endothelial cells (HUVECs). The effect on endothelial integrity was assessed both on the morphological (fluorescent immunocytochemistry for VE-cadherin and F-actin) and functional (transendothelial electrical resistance (TER)) level that was recorded in real time with an "electric cell-substrate impedance sensing" (ECIS) system (ibidi). We found (1) severe alterations of cell-cell contacts and the cytoskeletal architecture and (2) profound functional permeability changes, the putative cellular correlate of the clinical vascular leakage syndrome. However, the endothelial barrier was protected from these profound adverse effects when HUVECs were challenged with septic shock serum that was collected after extracorporeal cytokine removal.
  
  
  CONCLUSIONS
  Beneficial observations of extracorporeal cytokine removal in septic shock patients might-at least in part-be promoted via protection of vascular barrier function.
authors.affiliation: Department of Medicine, Division of Nephrology & Hypertension, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: David
authors.affiliation: Department of Medicine, Division of Nephrology & Hypertension, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Thamm
authors.affiliation: Department of Medicine, Division of Nephrology & Hypertension, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Bernhard M W
authors.initials: BMW
authors.lastname: Schmidt
authors.affiliation: Institute of Transplant Immunology, IFB-Tx, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Christine S
authors.initials: CS
authors.lastname: Falk
authors.affiliation: Department of Medicine, Division of Nephrology & Hypertension, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Jan T
authors.initials: JT
authors.lastname: Kielstein
keywords: Cytokines; Endothelial permeability; Extracorporeal removal; Sepsis; Vascular leakage