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.
Citation
ID:
281472
Ref Key:
brady2016personalized