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.

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Author:Philipp StörmannORCiDGND, Nils Becker, Jan Tilmann VollrathORCiDGND, Kernt KöhlerGND, Andrea JanicováGND, Sebastian WutzlerGND, Frank HildebrandORCiDGND, Ingo MarziORCiDGND, Borna ReljaORCiDGND
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/31234556
Parent Title (English):Journal of Clinical Medicine
Place of publication:Basel
Document Type:Article
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
Issue:6, Art. 896
Page Number:15
First Page:1
Last Page:15
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
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0