Pulmonary inflammatory response and immunomodulation to multiple trauma and hemorrhagic shock in pigs.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2022
Historique:
received: 28 04 2022
accepted: 31 10 2022
entrez: 8 12 2022
pubmed: 9 12 2022
medline: 15 12 2022
Statut: epublish

Résumé

Patients suffering from severe trauma experience substantial immunological stress. Lung injury is a known risk factor for the development of posttraumatic complications, but information on the long-term course of the pulmonary inflammatory response and treatment with mild hypothermia are scarce. To investigate the pulmonary inflammatory response to multiple trauma and hemorrhagic shock in a porcine model of combined trauma and to assess the immunomodulatory properties of mild hypothermia. Following induction of trauma (blunt chest trauma, liver laceration, tibia fracture), two degrees of hemorrhagic shock (45 and 50%) over 90 (n = 30) and 120 min. (n = 20) were induced. Animals were randomized to hypothermia (33°C) or normothermia (38°C). We evaluated bronchoalveolar lavage (BAL) fluid and tissue levels of cytokines and investigated changes in microRNA- and gene-expression as well as tissue apoptosis. We observed a significant induction of Interleukin (IL) 1β, IL-6, IL-8, and Cyclooxygenase-2 mRNA in lung tissue. Likewise, an increased IL-6 protein concentration could be detected in BAL-fluid, with a slight decrease of IL-6 protein in animals treated with hypothermia. Lower IL-10 protein levels in normothermia and higher IL-10 protein concentrations in hypothermia accompanied this trend. Tissue apoptosis increased after trauma. However, intervention with hypothermia did not result in a meaningful reduction of pro-inflammatory biomarkers or tissue apoptosis. We observed signs of a time-dependent pulmonary inflammation and apoptosis at the site of severe trauma, and to a lower extent in the trauma-distant lung. Intervention with mild hypothermia had no considerable effect during 48 hours following trauma.

Sections du résumé

BACKGROUND
Patients suffering from severe trauma experience substantial immunological stress. Lung injury is a known risk factor for the development of posttraumatic complications, but information on the long-term course of the pulmonary inflammatory response and treatment with mild hypothermia are scarce.
AIM
To investigate the pulmonary inflammatory response to multiple trauma and hemorrhagic shock in a porcine model of combined trauma and to assess the immunomodulatory properties of mild hypothermia.
METHODS
Following induction of trauma (blunt chest trauma, liver laceration, tibia fracture), two degrees of hemorrhagic shock (45 and 50%) over 90 (n = 30) and 120 min. (n = 20) were induced. Animals were randomized to hypothermia (33°C) or normothermia (38°C). We evaluated bronchoalveolar lavage (BAL) fluid and tissue levels of cytokines and investigated changes in microRNA- and gene-expression as well as tissue apoptosis.
RESULTS
We observed a significant induction of Interleukin (IL) 1β, IL-6, IL-8, and Cyclooxygenase-2 mRNA in lung tissue. Likewise, an increased IL-6 protein concentration could be detected in BAL-fluid, with a slight decrease of IL-6 protein in animals treated with hypothermia. Lower IL-10 protein levels in normothermia and higher IL-10 protein concentrations in hypothermia accompanied this trend. Tissue apoptosis increased after trauma. However, intervention with hypothermia did not result in a meaningful reduction of pro-inflammatory biomarkers or tissue apoptosis.
CONCLUSION
We observed signs of a time-dependent pulmonary inflammation and apoptosis at the site of severe trauma, and to a lower extent in the trauma-distant lung. Intervention with mild hypothermia had no considerable effect during 48 hours following trauma.

Identifiants

pubmed: 36476845
doi: 10.1371/journal.pone.0278766
pii: PONE-D-22-12473
pmc: PMC9728855
doi:

Substances chimiques

Interleukin-10 130068-27-8
Interleukin-6 0

Banques de données

figshare
['10.6084/m9.figshare.21324561.v1']

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0278766

Informations de copyright

Copyright: © 2022 Oestreich et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Marc-Alexander Oestreich (MA)

Institute for Lung Research, Universities of Giessen and Marburg Lung Center, German Center for Lung Research (DZL), Philipps University Marburg, Marburg, Germany.

Kerstin Seidel (K)

Vascular Biology Section, Evans Department of Medicine, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, United States of America.

Wilhelm Bertrams (W)

Institute for Lung Research, Universities of Giessen and Marburg Lung Center, German Center for Lung Research (DZL), Philipps University Marburg, Marburg, Germany.

Hans-Helge Müller (HH)

Institute for Medical Bioinformatics and Biostatistics, Philipps-Universität Marburg, Marburg, Germany.

Martin Sassen (M)

Department of Anesthesia and Intensive Care Medicine, University Medical Center Gießen and Marburg, Philipps University Marburg, Marburg, Germany.
Center for Emergency Medicine, University Medical Center Gießen and Marburg, Philipps University Marburg, Marburg, Germany.

Thorsten Steinfeldt (T)

BG Unfallklinik Frankfurt am Main gGmbH, Department for Anesthesia, Intensive Care Medicine and Pain Therapy, Frankfurt am Main, Germany.

Hinnerk Wulf (H)

Department of Anesthesia and Intensive Care Medicine, University Medical Center Gießen and Marburg, Philipps University Marburg, Marburg, Germany.

Bernd Schmeck (B)

Institute for Lung Research, Universities of Giessen and Marburg Lung Center, German Center for Lung Research (DZL), Philipps University Marburg, Marburg, Germany.
Department of Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, German Center for Lung Research (DZL), Philipps University Marburg, Marburg, Germany.
Center for Synthetic Microbiology (SYNMIKRO), Philipps-University of Marburg, Marburg, Germany.
German Center for Infection Research (DZIF), Partner Site Giessen-Marburg-Langen, Marburg, Germany.

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