Targeting IL-1R1-Mediated Anemia in Complex Combat Related Burns
Abstract
Combat-related burns have largely been caused by explosions in recent conflicts and frequently overlapwith traumatic brain injury (TBI) diagnosis. The purpose of this study is to produce a preclinicalmodel of concomitant burn and blast induced TBI to understand the impact of the combined injury on theanemia of critical illness (ACI) and neuroinflammation and to validate IL-1R1 targeted therapies as anintervention. We have found no evidence that concomitant injury exacerbates systemic inflammation orACI compared to burn alone. Given ACI is primarily a consequence of burn in the combined injury model,and we recently reported IL-1/ blockade markedly attenuates post burn ACI, it is highly likely thetherapy will be effective in the combined injury model. We utilized RNAseq to determine if concomitantinjury amplifies neuroinflammation and identified transcriptional changes that reflect those induced byindividual injuries as well as several changes that are unique to concomitant injury. Lipocalin-2(Lcn2), a common inflammatory biomarker, demonstrated the largest fold change following concomitantinjury so we used Lcn2 expression as an endpoint for initial therapeutic studies. IL-1/ blockademarkedly attenuated systemic inflammation and Lcn2 expression in the brain following eitherprophylactic or therapeutic administration of the neutralizing antibodies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2023
- Accession Number
- AD1216098
Entities
People
- Jason S. Gardner
Organizations
- University of Cincinnati