title: An inhaled tumor necrosis factor-alpha-derived TIP peptide improves the pulmonary function in experimental lung injury.
abstract: BACKGROUND
  The lectin-like domain of TNF-α enhances the fluid clearance across the alveolar barrier. For experimental purposes, the lectin-like domain can be mimicked by a synthetic peptide representing the TIP-motif of TNF-α. The present study aims to assess the acute effect of TIP on the pulmonary function in a porcine model of acute respiratory distress syndrome (ARDS).
  
  
  METHODS
  Lung injury was induced in 16 pigs (25-27 kg) by bronchoalveolar lavage followed by injurious ventilation. Following randomisation, either nebulised TIP (1 mg/kg; AP301, APEPTICO, Vienna, Austria) or water for injection (control group) was administered. During 5 h of monitoring, the extravascular lung water index (EVLWI), the quotient of partial pressure of oxygen and inspired oxygen concentration (PaO(2) /FiO(2) ) and the pulmonary shunt fraction were repetitively assessed. The data were evaluated by an analysis of variance including Bonferroni-Holm correction.
  
  
  RESULTS
  Comparable baseline conditions in both groups were achieved. Ventilatory parameters were standardised in both groups. In the TIP group, a significant reduction of the EVLWI and a simultaneous increase in the PaO(2) /FiO(2)  ratio was shown (each P < 0.0001). No changes in the control group were observed (EVLWI: P = 0.43, PaO(2) /FiO(2) : P = 0.60). The intergroup comparison demonstrates a significant advantage of TIP inhalation over placebo (EVLWI: P < 0.0001, PaO(2) /FiO(2) : P = 0.004, shunt fraction: P = 0.0005).
  
  
  CONCLUSIONS
  The inhalation of TIP induces an amelioration of clinical surrogate parameters of the lung function in a porcine lung injury model. By mimicking the lectin-like domain, the synthetic TIP peptide AP301 is an innovative approach as supportive therapy in ARDS.
authors.affiliation: Department of Anaesthesiology, Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, Mainz, Germany. hartmane@uni-mainz.de
authors.forename: E K
authors.initials: EK
authors.lastname: Hartmann
authors.forename: S
authors.initials: S
authors.lastname: Boehme
authors.forename: B
authors.initials: B
authors.lastname: Duenges
authors.forename: A
authors.initials: A
authors.lastname: Bentley
authors.forename: K U
authors.initials: KU
authors.lastname: Klein
authors.forename: R
authors.initials: R
authors.lastname: Kwiecien
authors.forename: C
authors.initials: C
authors.lastname: Shi
authors.forename: M
authors.initials: M
authors.lastname: Szczyrba
authors.forename: M
authors.initials: M
authors.lastname: David
authors.forename: K
authors.initials: K
authors.lastname: Markstaller
mesh_terms: D000818:Animals; D018893:Bronchoalveolar Lavage; D015633:Extravascular Lung Water / Q000502:physiology; D006439:Hemodynamics / Q000502:physiology; D008168:Lung / Q000187:drug effects*; D055370:Lung Injury / Q000188:drug therapy* / Q000503:physiopathology; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D010446:Peptide Fragments / Q000737:chemistry / Q000627:therapeutic use*; D012121:Respiration, Artificial; D012128:Respiratory Distress Syndrome / Q000188:drug therapy / Q000503:physiopathology; D012129:Respiratory Function Tests; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; D010100:Oxygen