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

arXiv · 1609.01570

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

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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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BibTeX RIS

Renee Brady, Dennis O. Frank-Ito, Hien T. Tran, Susanne Janum, Kirsten Møller, Susanne Brix, Johnny T. Ottesen, Jesper Mehlsen, Mette S. Olufsen. 2016-09-06. Personalized Mathematical Model Predicting Endotoxin-Induced Inflammatory Responses in Young Men. https://arxiv.org/abs/1609.01570

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