title: Cytokine expression profile in human lungs undergoing normothermic ex-vivo lung perfusion.
abstract: BACKGROUND
  A donor lung shortage prevents patients from receiving life-saving transplants. Ex-vivo lung perfusion (EVLP) is a viable means of expanding the donor pool by evaluating and potentially improving donor lung function. The metabolic and inflammatory effects of EVLP on human lung tissue are currently unknown. We sought to establish representative cytokine expression in human donor lungs meeting acceptable lung transplant criteria after prolonged normothermic EVLP.
  
  
  METHODS
  Seven single human lungs not meeting traditional transplantation criteria for various reasons underwent normothermic EVLP. Lungs were perfused with deoxygenated colloid, rewarmed, and ventilated per standard protocol. Lung function was evaluated every hour. Biopsies were taken at 1, 6, and 12 hours. Inflammatory cytokines were quantitatively measured using a human cytokine magnetic bead-based multiplex assay.
  
  
  RESULTS
  All lungs met traditional transplant criteria after EVLP. The partial pressure of arterial oxygen and physiologic lung function significantly improved (p<0.05). No pulmonary edema was formed, and histology demonstrated no evidence of acute lung injury. Interleukin (IL)-6, IL-8, granulocyte colony-stimulating factor, and monocyte chemotactic protein-1 were upregulated, while granulocyte macrophage colony-stimulating factor was downregulated during EVLP (p<0.05). IL-1β, IL-4, IL-7, IL-12, interferon-γ, macrophage inflammatory protein-1β, and tumor necrosis factor-α were detectable and unchanged.
  
  
  CONCLUSIONS
  Ex-vivo lung perfusion demonstrates the ability to improve oxygenation and physiologic lung function in donor lungs unacceptable for transplantation without injury to the lung. We establish here a cytokine expression profile in human lungs undergoing normothermic EVLP. These data can be used in the future to explore novel targeted therapies for ischemia-reperfusion injury.
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado 80045, USA.
authors.forename: Miral R
authors.initials: MR
authors.lastname: Sadaria
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Smith
authors.forename: David A
authors.initials: DA
authors.lastname: Fullerton
authors.forename: George A
authors.initials: GA
authors.lastname: Justison
authors.forename: Joon H
authors.initials: JH
authors.lastname: Lee
authors.forename: Ferenc
authors.initials: F
authors.lastname: Puskas
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Grover
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Cleveland
authors.forename: T Brett
authors.initials: TB
authors.lastname: Reece
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Weyant
mesh_terms: D001706:Biopsy; D016207:Cytokines / Q000097:blood*; D006801:Humans; D008168:Lung / Q000098:blood supply*; D016040:Lung Transplantation / Q000276:immunology* / Q000473:pathology; D010101:Oxygen Consumption / Q000502:physiology; D010477:Perfusion / Q000379:methods*; D011379:Prognosis; D011651:Pulmonary Artery / Q000276:immunology / Q000473:pathology; D011654:Pulmonary Edema / Q000276:immunology / Q000473:pathology; D015427:Reperfusion Injury / Q000276:immunology* / Q000473:pathology; D014019:Tissue Donors / Q000600:supply & distribution*; D009927:Tissue and Organ Procurement / Q000379:methods; D014655:Vascular Resistance / Q000502:physiology; D052096:Warm Ischemia / Q000379:methods*
chemical_list: D016207:Cytokines