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Autoren: Hartmann, Erik
Ziebart, Alexander
Thomas, Rainer
Liu, Tanghua
Schad, Arno
Tews, Martha
Moosmann, Bernd
Kamuf, Jens
Duenges, Bastian
Thal, Serge
David, Matthias
Titel: Inhalation therapy with the synthetic TIP-like peptide AP318 attenuates pulmonary inflammation in a porcine sepsis model
Online-Publikationsdatum: 21-Okt-2022
Erscheinungsdatum: 2015
Sprache des Dokuments: Englisch
Zusammenfassung/Abstract: BACKGROUND: The lectin-like domain of TNF-alpha can be mimicked by synthetic TIP peptides and represents an innovative pharmacologic option to treat edematous respiratory failure. TIP inhalation was shown to reduce pulmonary edema and improve gas exchange. In addition to its edema resolution effect, TIP peptides may exert some anti-inflammatory properties. The present study therefore investigates the influence of the inhaled TIP peptide AP318 on intrapulmonary inflammatory response in a porcine model of systemic sepsis. METHODS: In a randomized-blinded setting lung injury was induced in 18 pigs by lipopolysaccharide-infusion and a second hit with a short period of ventilator-induced lung stress, followed by a six-hour observation period. The animals received either two inhalations with the peptide (AP318, 2x1 mg kg(-1)) or vehicle. Post-mortem pulmonary expression of inflammatory and mechanotransduction markers were determined by real-time polymerase chain reaction (IL-1beta, IL-6, TNF-alpha, COX-2, iNOS, amphiregulin, and tenascin-c). Furthermore, regional histopathological lung injury, edema formation and systemic inflammation were quantified. RESULTS: Despite similar systemic response to lipopolysaccharide infusion in both groups, pulmonary inflammation (IL-6, TNF-alpha, COX-2, tenascin-c) was significantly mitigated by AP318. Furthermore, a Western blot analysis shows a significantly lower of COX-2 protein level. The present sepsis model caused minor lung edema formation and moderate gas exchange impairment. Six hours after onset pathologic scoring showed no improvement, while gas exchange parameters and pulmonary edema formation were similar in the two groups. CONCLUSION: In summary, AP318 significantly attenuated intrapulmonary inflammatory response even without the presence or resolution of severe pulmonary edema in a porcine model of systemic sepsis-associated lung injury. These findings suggest an anti-inflammatory mechanism of the lectin-like domain beyond mere edema reabsorption in endotoxemic lung injury in vivo.
DDC-Sachgruppe: 610 Medizin
610 Medical sciences
Veröffentlichende Institution: Johannes Gutenberg-Universität Mainz
Organisationseinheit: FB 04 Medizin
Veröffentlichungsort: Mainz
ROR: https://ror.org/023b0x485
DOI: http://doi.org/10.25358/openscience-8139
Version: Published version
Publikationstyp: Zeitschriftenaufsatz
Nutzungsrechte: CC BY
Informationen zu den Nutzungsrechten: https://creativecommons.org/licenses/by/4.0/
Zeitschrift: BMC pulmonary medicine
15
Seitenzahl oder Artikelnummer: Art. 7
Verlag: BioMed Central
Verlagsort: London
Erscheinungsdatum: 2015
ISSN: 1471-2466
URL der Originalveröffentlichung: http://dx.doi.org/10.1186/s12890-015-0002-6
DOI der Originalveröffentlichung: 10.1186/s12890-015-0002-6
Enthalten in den Sammlungen:DFG-OA-Publizieren (2012 - 2017)

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