Format

Send to

Choose Destination
See comment in PubMed Commons below
Acta Anaesthesiol Scand. 2013 Mar;57(3):334-41. doi: 10.1111/aas.12034. Epub 2012 Dec 6.

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

Author information

1
Department of Anaesthesiology, Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, Mainz, Germany. hartmane@uni-mainz.de

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.

PMID:
23216436
DOI:
10.1111/aas.12034
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley
    Loading ...
    Support Center