Personalized Mathematical Model Predicting Endotoxin-Induced Inflammatory Responses in Young Men

Personalized Mathematical Model Predicting Endotoxin-Induced Inflammatory Responses in Young Men

Renee Brady; Dennis O. Frank-Ito; Hien T. Tran; Susanne Janum; Kirsten Møller; Susanne Brix; Johnny T. Ottesen; Jesper Mehlsen; Mette S. Olufsen
Journal not set 2016
19
brady2016personalized

Abstract

The initial reaction of the body to pathogenic microbial infection or severe tissue trauma is an acute inflammatory response. The magnitude of such a response is of critical importance, since an uncontrolled response can cause further tissue damage, sepsis, and ultimately death, while an insufficient response can result in inadequate clearance of pathogens. A normal inflammatory response helps to annihilate threats posed by microbial pathogenic ligands, such as endotoxins, and thus, restore the body to a healthy state. Using a personalized mathematical model, comprehension and a detailed description of the interactions between pro- and anti-inflammatory cytokines can provide important insight in the evaluation of a patient with sepsis or a susceptible patient in surgery. Our model is calibrated to experimental data obtained from experiments measuring pro-inflammatory cytokines (interleukin-6 (IL-6), tumor necrosis factor (TNF-), and chemokine ligand-8 (CXCL8)) and the anti-inflammatory cytokine interleukin-10 (IL-10) over 8 hours in 20 healthy young male subjects, given a low dose intravenous injection of lipopolysaccharide (LPS), resulting in endotoxin-stimulated inflammation. Through the calibration process, we created a personalized mathematical model that can accurately determine individual differences between subjects, as well as identify those who showed an abnormal response.

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