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

Introduction The lectin-like domain of TNF- 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-. 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 (2527kg) by bronchoalveolar lavage followed by injurious ventilation. Following randomisation, either nebulised TIP (1mg/kg; AP301, APEPTICO, Vienna, Austria) or water for injection (control group) was administered. During 5h of monitoring, the extravascular lung water index (EVLWI), the quotient of partial pressure of oxygen and inspired oxygen concentration (PaO2/FiO2) and the pulmonary shunt fraction were repetitively assessed. The data were evaluated by an analysis of variance including BonferroniHolm 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 PaO2/FiO2 ratio was shown (each P<0.0001). No changes in the control group were observed (EVLWI: P=0.43, PaO2/FiO2: P=0.60). The intergroup comparison demonstrates a significant advantage of TIP inhalation over placebo (EVLWI: P<0.0001, PaO2/FiO2: 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.