An inhaled tumor necrosis factor-alpha-derived TIP peptide improves the pulmonary function in experimental lung injury.

Abstract

INTRODUCTION:

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: E K Hartmann, S Boehme, B Duenges, A Bentley, K U Klein, R Kwiecien, C Shi, M Szczyrba, M David, K Markstaller
• Journal: Acta anaesthesiologica Scandinavica (Acta Anaesthesiol Scand) Vol. 57 Issue 3 Pg. 334-41 (Mar 2013) ISSN: 1399-6576 [Electronic] England
• PMID: 23216436 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 The Acta Anaesthesiologica Scandinavica Foundation.

Chemical References

• Peptide Fragments
• Tumor Necrosis Factor-alpha
• Oxygen

Topics

• Animals
• Bronchoalveolar Lavage
• Extravascular Lung Water (physiology)
• Hemodynamics (physiology)
• Lung (drug effects)
• Lung Injury (drug therapy, physiopathology)
• Oxygen (blood)
• Partial Pressure
• Peptide Fragments (chemistry, therapeutic use)
• Respiration, Artificial
• Respiratory Distress Syndrome (drug therapy, physiopathology)
• Respiratory Function Tests
• Swine
• Tumor Necrosis Factor-alpha (chemistry, therapeutic use)