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Monotrauma is associated with enhanced remote inflammatory response and organ damage, while polytrauma intensifies both in porcine trauma model

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Abstract

Aim

Severely injured patients experience substantial immunological stress upon traumatic insult. Next to the direct local tissue injury also other organs, which are not directly injured such as liver and lung, are frequently affected by a so-called remote organ damage (ROD) after trauma. Thus, we studied the inflammatory response of lung and liver either after isolated femur fracture as example for ROD, or after multiple trauma in a porcine polytrauma model.

Methods

Twenty-four male pigs (Sus scrofa) underwent either isolated standardized femoral fracture (monotrauma, MT, n = 12) or polytrauma (PT, n = 12). PT consisted of a femur fracture, lung contusion, liver laceration, hemorrhagic shock, subsequent resuscitation and surgical fracture fixation. Six animals served as controls (sham). After 72 h inflammatory changes were determined by analyses of the interleukin (IL)-6 gene expression and tissue infiltration of polymorphonuclear leukocyte (PMN, myeloperoxidase staining). ROD in MT, and lung as well as liver damage in PT were assessed histologically by hematoxylin–eosin staining. Expression of phosphorylated p65 NF-κB was evaluated by immunohistology.

Results

IL-6 increased in lungs and liver in both groups MT and PT, respectively, compared to sham. Similarly, PMN infiltration of the lungs and liver increased significantly after both MT and PT compared to sham. Histological evaluation demonstrated tissue damage notably in lungs after MT, while tissue damage after PT was found in both lung and liver after PT. p65 NF-κB tended to an increase upon MT, and was significantly enhanced after PT in both tissues.

Conclusion

Our data indicate that remote organ damage after MT notably in lungs was associated with an enhanced inflammatory response. Severe polytrauma substantially intensifies this response and organ damage in the underlying model.

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Acknowledgements

We thank Katrin Jurida, Kerstin Kontradowitz and Alexander Schaible for outstanding technical assistance. Furthermore, the authors thank Lukas Schimunek, Rafael Serve, Yannik Kalbas and Hannah Lüken for their assistance in conducting the animal experiments. We also thank Thaddeus Stopinski for his considerable support during the entire study. This work was supported by the Arbeitsgemeinschaft für Osteosynthesefragen (AO) Foundation (S-14-14P). TREAT Research Group: P. Störmann1, B. Auner1, B. Relja1, I. Marzi1, T-P. Simon2, G. Marx2, A. Haug3, L. Egerer3, M. v. Griensven3, M. Kalbitz4, M. Huber-Lang5, R. Tolba6, K. Reiss7, S. Uhlig7, K. Horst8, M. Teuben9, R. Pfeifer9, H.C. Pape9, F. Hildebrand8: 1Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe University, Frankfurt/Main, Germany; 2Department of Intensive Care and Intermediate Care, RWTH Aachen University, Germany; 3Department of Trauma Surgery, Technical University Munich, Germany; 4Department of Orthopedic Trauma, Hand, Plastic, and Reconstructive Surgery, University of Ulm, Germany; 5Institute of Clinical and Experimental Trauma-Immunology, University Hospital, Ulm, Germany; 6Institute for Laboratory Animal Science and Experimental Surgery, RWTH Aachen University, Germany; 7Institute of Pharmacology and Toxicology, RWTH Aachen University, Germany; 8Department of Orthopaedic Trauma, RWTH Aachen University, Germany; 9Department of Orthopaedic Trauma Surgery, University Hospital Zurich, University of Zurich, Switzerland.

Funding

Project no. S-14-14P was supported by the AO Foundation.

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Author notes

  1. Philipp Störmann and Nils Wagner contributed equally.

Authors and Affiliations

  1. Department of Trauma, Hand and Reconstructive Surgery, University Hospital of the Goethe-University Frankfurt, 60590, Frankfurt, Germany

    Philipp Störmann, Nils Wagner, Birgit Auner, Sebastian Wutzler, Ingo Marzi & Borna Relja

  2. Institute of Veterinary Pathology, Justus Liebig University Giessen, Giessen, Germany

    Kernt Köhler

  3. Department of Intensive Care and Intermediate Care, RWTH Aachen University, Aachen, Germany

    Tim-P. Simon

  4. Department of Orthopaedic Trauma Surgery, University Hospital Zurich, University of Zurich, Zurich, Switzerland

    Roman Pfeifer & Hans-Christoph Pape

  5. Department of Orthopaedic Trauma, RWTH Aachen University, Aachen, Germany

    Klemens Horst & Frank Hildebrand

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  1. Philipp Störmann
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Contributions

PS, NW and BR designed the study, performed the experiments and performed the statistical analyses and wrote the manuscript. PS, BA, TPS, RP and KH performed the experiments with the pigs. KK performed the histological analyses. KK, HCP, SW and IM made important intellectual contributions to the study and revised the manuscript.

Corresponding author

Correspondence to Borna Relja.

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Conflict of interest

The authors declare that there is no conflict of interest regarding the publication of this paper.

Ethics approval

The ethical approval for the study was obtained by the “Landesamt für Natur-, Umwelt- und Verbraucherschutz, Nordrhein Westfalen” (LANUV-NRW), Recklinghausen, Germany, which is the local responsible government authority (ethical permission: AZ TV-Nr.: 82-02.04.2014.A265).

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Consent to submit has been received from all co-authors.

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All data generated or analysed during this study are included in this published article. The data are available from the corresponding author on reasonable request.

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Störmann, P., Wagner, N., Köhler, K. et al. Monotrauma is associated with enhanced remote inflammatory response and organ damage, while polytrauma intensifies both in porcine trauma model. Eur J Trauma Emerg Surg 46, 31–42 (2020). https://doi.org/10.1007/s00068-019-01098-1

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