Manipulating the Macrophage Iron Hepcidin Axis to Prevent Acute Lung Injury/Acute Respiratory Distress Syndrome Secondary to Severe Trauma and Hemorrhagic Shock
Abstract
During the reporting period, we have established a mouse model of polytrauma (hemorrhagic shock with laparotomy and cecectomy) that consistently induces systemic inflammation and have developed and validated a method for the non-invasive administration of intratracheal drugs, which we will use to deliver intratracheal lipopolysaccharide (LPS). Our studies in mice lacking the hepcidin gene support our principal hypothesis that increased intracellular iron levels are associated with a more robust inflammatory response. We have also tested multiple iron chelators for their anti-inflammatory properties, showing that defer prone and pyridoxal isonicotinoyl hydrazone (PIH) are at least as effective as deferoxamine at blunting the acute inflammatory response, at lower concentrations. Taken together, our data strongly suggest a critical role for intracellular iron in acute inflammation. We are well placed to continue the project to test the efficacy of iron chelators in a two-hit murine model of polytrauma followed by endotoxin induced lung injury.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2018
- Accession Number
- AD1060405
Entities
People
- Aranya Bagchi
Organizations
- Massachusetts General Hospital