TY - JOUR A1 - Störmann, Philipp A1 - Becker, Nils A1 - Vollrath, Jan Tilmann A1 - Köhler, Kernt A1 - Janicová, Andrea A1 - Wutzler, Sebastian A1 - Hildebrand, Frank A1 - Marzi, Ingo A1 - Relja, Borna T1 - Early local inhibition of club cell protein 16 following chest trauma reduces late sepsis-induced acute lung injury T2 - Journal of Clinical Medicine N2 - 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. KW - uteroglobin KW - CC16 KW - inflammation KW - chest trauma KW - acute lung injury (ALI) Y1 - 2019 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/51070 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-510707 SN - 2077-0383 N1 - 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 VL - 8 IS - 6, Art. 896 SP - 1 EP - 15 PB - MDPI CY - Basel ER -