Early local inhibition of club cell protein 16 following chest trauma reduces late sepsis-induced acute lung injury
- Blunt thoracic trauma (TxT) deteriorates clinical post-injury outcomes. Ongoing inflammatory changes promote the development of post-traumatic complications, frequently causing Acute Lung Injury (ALI). Club Cell Protein (CC)16, a pulmonary anti-inflammatory protein, correlates with lung damage following TxT. Whether CC16-neutralization influences the inflammatory course during ALI is elusive. Ninety-six male CL57BL/6N mice underwent a double hit model of TxT and cecal ligation puncture (CLP, 24 h post-TxT). Shams underwent surgical procedures. CC16 was neutralized by the intratracheal application of an anti-CC16-antibody, either after TxT (early) or following CLP (late). Euthanasia was performed at 6 or 24 h post-CLP. Systemic and pulmonary levels of IL-6, IL-1β, and CXCL5 were determined, the neutrophils were quantified in the bronchoalveolar lavage fluid, and histomorphological lung damage was assessed. ALI induced a significant systemic IL-6 increase among all groups, while the local inflammatory response was most prominent after 24 h in the double-hit groups as compared to the shams. Significantly increased neutrophilic infiltration upon double hit was paralleled with the enhanced lung damage in all groups as compared to the sham, after 6 and 24 h. Neutralization of CC16 did not change the systemic inflammation. However, early CC16-neutralization increased the neutrophilic infiltration and lung injury at 6 h post-CLP, while 24 h later, the lung injury was reduced. Late CC16-neutralization increased neutrophilic infiltration, 24 h post-CLP, and was concurrent with an enhanced lung injury. The data confirmed the anti-inflammatory potential of endogenous CC16 in the murine double-hit model of ALI.
Author: | Philipp StörmannORCiDGND, Nils Becker, Jan Tilmann VollrathORCiDGND, Kernt Köhler, Andrea Janicova, Sebastian WutzlerGND, Frank Hildebrand, Ingo MarziORCiDGND, Borna ReljaORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-510707 |
DOI: | https://doi.org/10.3390/jcm8060896 |
ISSN: | 2077-0383 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/31234556 |
Parent Title (English): | Journal of Clinical Medicine |
Publisher: | MDPI |
Place of publication: | Basel |
Document Type: | Article |
Language: | English |
Year of Completion: | 2019 |
Date of first Publication: | 2019/06/22 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2019/09/19 |
Tag: | CC16; acute lung injury (ALI); chest trauma; inflammation; uteroglobin |
Volume: | 8 |
Issue: | 6, Art. 896 |
Page Number: | 15 |
First Page: | 1 |
Last Page: | 15 |
Note: | This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited |
HeBIS-PPN: | 454154194 |
Institutes: | Medizin / Medizin |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Open-Access-Publikationsfonds: | Medizin |
Licence (German): | ![]() |