Resuscitation Using Elemental Reducing Agents
Abstract
PROJECT ABSTRACT: Publically releasable Resuscitation Using Elemental Reducing Agents Traumatic injuries cause excessive immune activity lasting for days that can result in systemic inflammatory response syndrome (SIRS) and death. The early post-trauma phase is followed by a period of reduced immune function and inability to mount an appropriate inflammatory response, often leading to death from otherwise non-lethal bacterial and viral infections (figure 1). For decades physicians have attempted to manage immune activity by reducing the early hyperinflammation phase (SIRS) and/or by augmenting immune activity during the later immunosuppression phase. An integrated method to limit both the initial hyperinflammation and later hypoinflammation is needed to maintain immune homeostasis during trauma. This proposal is designed to test the hypothesis that a group of redox active anions that we refer to as Elemental Reducing Agents (ERAs) including, bromide, iodide, selenide and sulfide, can be used to maintain immune homeostasis. We found that iodine redistributes naturally during trauma leading to increased blood iodide. Within 2 hours of severe blunt force trauma (early phase), blood iodide increases by 17-fold and it increases by more than 25-fold in the second phase of trauma (hypoinflammatory/sepsis). We also found that therapeutic administration of additional iodide to further increase the concentration in blood significantly improves outcome in early phase trauma and also blocks thyroid hormone turnover. We hypothesize that blocking this turnover may preserve the ability to mount an appropriate immune response to subsequent infection. One possible mechanism by which iodide may suppress inflammation is its ability to catalytically destroy hydrogen peroxide, the driver of inflammation. Our goal with this grant application is to address the two-stage conundrum facing trauma patients and their physicians to maintain immune homeostasis during both the early hyperinflammation phase that causes tissue damage from too much hydrogen peroxide and the later phase when hydrogen peroxide is required to deal with nosocomial infection. Our hypothesis is that early administration of therapeutic iodide will both degrade excessive hydrogen peroxide in the first phase of trauma and preserve thyroid hormone reserves which are necessary to generate hydrogen peroxide used fight off later nosocomial infection. We propose to: 1. Determine whether iodide improves outcome in the second immunosuppression phase of injury. 2. Further define the mechanism by which ERAs provide benefit in trauma. 3. Identify other redistributed ERAs and test whether they also improve outcome in trauma. The development of ERA technology represents an opportunity to improve treatment of both civilian and combat patients suffering from trauma. Studies have shown that iodide is incredibly safe for use in humans and could be safely administered even by front-line medics in conflict zones.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jun 25, 2021
- Source ID
- W911NF2110191
Entities
People
- Mark Roth
Organizations
- Army Contracting Command
- Fred Hutchinson Cancer Center
- United States Army