Modeling of the Acute Inflammatory Response Following Injury

The purpose of this research study is to gather clinical and biologic information from severely injured patients to better understand and characterize the host response to injury and inflammation across several domains. This information may improve outcome prediction, improve clinical treatment of injured patients, and permit the construction of non-biologic computerized models of illness that can be utilized to represent the host response in future research efforts. This study is designed as the calibration of a mathematical model of this response with predictive capabilities. The central hypothesis governing this study is that adaptive immune elements are crucial to determining the outcome of complex inflammatory scenarios. We propose to test these hypotheses in the following interrelated Specific Aims: Specific Aim 1: To develop a robust mathematical model describing trauma/hemorrhage-induced inflammation in humans, its pathologic consequences, and possible therapies. Specific Aim 2: To translate the mathematical model to humans and create software aimed at individualized clinical decision-making. Specific Aim 3: To determine the prevalence of an IL-1 receptor-associated kinase (IRAK-1) variant haplotype located on the X-chromosome in an injured population, and to characterize differences in the pro-inflammatory response across gender, relative to the IRAK-1 haplotype. Specific Aim 4: To determine if increased arginase activity previously observed in isolated peripheral blood mononuclear cells of trauma patients is a consequence of the presence of contaminating activated granulocytes or a particular subset of an arginase positive monocyte subset.