Eritoran attenuates tissue damage and inflammation in hemorrhagic shock/trauma
Background - Severe injury and associated hemorrhagic shock lead to an inflammatory response and subsequent increased tissue damage. Numerous reports have shown that injury-induced inflammation and the associated end-organ damage is driven by Toll-like receptor 4 (TLR4) activation via damage-associa...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
27 March 2013
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| In: |
Journal of surgical research
Year: 2013, Volume: 184, Issue: 2, Pages: e17-e25 |
| ISSN: | 1095-8673 |
| DOI: | 10.1016/j.jss.2013.03.023 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.jss.2013.03.023 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0022480413002187 
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| Author Notes: | Sebastian Korff, Patricia Loughran, Chanchun Cai, Yi Shan Lee, Melanie Scott, and Timothy R. Billiar, MD |
| Summary: | Background - Severe injury and associated hemorrhagic shock lead to an inflammatory response and subsequent increased tissue damage. Numerous reports have shown that injury-induced inflammation and the associated end-organ damage is driven by Toll-like receptor 4 (TLR4) activation via damage-associated molecular patterns. We examined the effectiveness of Eritoran tetrasodium (E5564), an inhibitor of TLR4 function, in reducing inflammation induced during hemorrhagic shock with resuscitation (HS/R) or after peripheral tissue injury (bilateral femur fracture, BFF). - Material and methods - Mice underwent HS/R or BFF with or without injection of Eritoran (5 mg/kg body weight) or vehicle control given before, both before and after, or only after HS/R or BFF. Mice were sacrificed after 6 h and plasma and tissue cytokines, liver damage (histology; aspartate aminotransferase/alanine aminotransferase), and inflammation (NF-κB) and gut permeability were assessed. - Results - In HS/R Eritoran significantly reduced liver damage (values ± SEM: alanine aminotransferase 9910 ± 3680 U/L versus 1239 ± 327 U/L and aspartate aminotransferase 5863 ± 2000 U/L versus 1246 ± 243 U/L, P < 0.01) at 6 h compared with control when given just before HS and again just prior to resuscitation. Eritoran administration also led to lower IL-6 levels in plasma and liver and less NF-κB activation in liver. Increases in gut barrier permeability induced by HS/R were also prevented with Eritoran. Eritoran similarly diminished BFF-mediated systemic inflammatory responses. - Conclusion - These data suggest Eritoran can inhibit tissue damage and inflammation induced via TLR4/myeloid differentiation factor 2 signaling from damage-associated molecular patterns released during HS/R or BFF. Eritoran may represent a promising therapeutic for trauma patients to prevent multiple organ failure. |
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| Item Description: | Gesehen am 01.12.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1095-8673 |
| DOI: | 10.1016/j.jss.2013.03.023 |