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

作者: E. K. HARTMANN , S. BOEHME , B. DUENGES , A. BENTLEY , K. U. KLEIN

DOI: 10.1111/AAS.12034

关键词:

摘要: INTRODUCTION The lectin-like domain of TNF-α enhances the fluid clearance across alveolar barrier. For experimental purposes, can be mimicked by a synthetic peptide representing TIP-motif TNF-α. present study aims to assess acute effect TIP on pulmonary function in porcine model respiratory distress syndrome (ARDS). METHODS Lung injury was induced 16 pigs (25-27 kg) bronchoalveolar lavage followed injurious ventilation. Following randomisation, either nebulised (1 mg/kg; AP301, APEPTICO, Vienna, Austria) or water for injection (control group) administered. During 5 h monitoring, extravascular lung index (EVLWI), quotient partial pressure oxygen and inspired concentration (PaO(2) /FiO(2) ) shunt fraction were repetitively assessed. data evaluated an analysis variance including Bonferroni-Holm correction. RESULTS Comparable baseline conditions both groups achieved. Ventilatory parameters standardised groups. In group, significant reduction EVLWI simultaneous increase PaO(2) ratio shown (each P < 0.0001). No changes control group observed (EVLWI: P = 0.43, : P = 0.60). intergroup comparison demonstrates advantage inhalation over placebo P < 0.0001, P = 0.004, fraction: P = 0.0005). CONCLUSIONS induces amelioration clinical surrogate model. By mimicking domain, AP301 is innovative approach as supportive therapy ARDS.

参考文章(37)
Anna Börjesson, Andreas Norlin, Xiangdong Wang, Roland Andersson, Hans G. Folkesson, TNF-α stimulates alveolar liquid clearance during intestinal ischemia-reperfusion in rats American Journal of Physiology-lung Cellular and Molecular Physiology. ,vol. 278, ,(2000) , 10.1152/AJPLUNG.2000.278.1.L3
Matthay M, Lewis Fr, Mackersie Rc, Bongard Fs, Morphologic and physiologic correlates of increased extravascular lung water. Surgery. ,vol. 96, pp. 395- 403 ,(1984)
R. J. Keenan, T. R. Todd, W. Demajo, A. S. Slutsky, Effects of hypercarbia on arterial and alveolar oxygen tensions in a model of gram-negative pneumonia Journal of Applied Physiology. ,vol. 68, pp. 1820- 1825 ,(1990) , 10.1152/JAPPL.1990.68.5.1820
Leland Dobbs, Meshell Johnson, Jeff Vanderbilt, Lennell Allen, Robert Gonzalez, The great big alveolar TI cell: evolving concepts and paradigms. Cellular Physiology and Biochemistry. ,vol. 25, pp. 55- 62 ,(2010) , 10.1159/000272063
R Lucas, S Magez, R De Leys, L Fransen, J. Scheerlinck, M Rampelberg, E Sablon, P De Baetselier, Mapping the lectin-like activity of tumor necrosis factor. Science. ,vol. 263, pp. 814- 817 ,(1994) , 10.1126/SCIENCE.8303299
István Vadász, Ralph T. Schermuly, Hossein A. Ghofrani, Sebastian Rummel, Susan Wehner, Inge Mühldorfer, Klaus P. Schäfer, Werner Seeger, Rory E. Morty, Friedrich Grimminger, Norbert Weissmann, The lectin-like domain of tumor necrosis factor-α improves alveolar fluid balance in injured isolated rabbit lungs* Critical Care Medicine. ,vol. 36, pp. 1543- 1550 ,(2008) , 10.1097/CCM.0B013E31816F485E
Sharadindu Rai, Doreen Engelberts, John G Laffey, Charles Frevert, Osamu Kajikawa, Thomas R Martin, Martin Post, Brian P Kavanagh, Therapeutic hypercapnia is not protective in the in vivo surfactant-depleted rabbit lung. Pediatric Research. ,vol. 55, pp. 42- 49 ,(2004) , 10.1203/01.PDR.0000098502.72182.55
Guang Yang, Boris Gorshkov, Supriya Sridhar, Alexander Verin, Rudolf Lucas, Jürg Hamacher, Richard White, Trinad Chakraborty, The dual role of TNF in pulmonary edema Journal of cardiovascular disease research. ,vol. 1, pp. 29- 36 ,(2010) , 10.4103/0975-3583.59983
István Vadász, Rory E. Morty, Markus G. Kohstall, Andrea Olschewski, Friedrich Grimminger, Werner Seeger, Hossein A. Ghofrani, Oleic acid inhibits alveolar fluid reabsorption: a role in acute respiratory distress syndrome? American Journal of Respiratory and Critical Care Medicine. ,vol. 171, pp. 469- 479 ,(2005) , 10.1164/RCCM.200407-954OC
Jürg Hamacher, Uz Stammberger, Jeremie Roux, Sanjiv Kumar, Guang Yang, Chenling Xiong, Ralph A. Schmid, Richard M. Fakin, Trinad Chakraborty, Hamid M. D. Hossain, Jean-François Pittet, Albrecht Wendel, Stephen M. Black, Rudolf Lucas, The lectin-like domain of tumor necrosis factor improves lung function after rat lung transplantation—Potential role for a reduction in reactive oxygen species generation* Critical Care Medicine. ,vol. 38, pp. 871- 878 ,(2010) , 10.1097/CCM.0B013E3181CDF725