TY  - JOUR
AU  - Parker, Robert
AU  - Hogg, Justin
AU  - Roy, Anirban
AU  - Kellum, John
AU  - Rimmelé, Thomas
AU  - Daun-Gruhn, Silvia
AU  - Fedorchak, Morgan
AU  - Valenti, Isabella
AU  - Federspiel, William
AU  - Rubin, Jonathan
AU  - Vodovotz, Yoram
AU  - Lagoa, Claudio
AU  - Clermont, Gilles
TI  - Modeling and Hemofiltration Treatment of Acute Inflammation
JO  - Processes
VL  - 4
IS  - 4
SN  - 2227-9717
CY  - Basel
PB  - MDPI
M1  - FZJ-2017-00246
SP  - 38 -
PY  - 2016
AB  - The body responds to endotoxins by triggering the acute inflammatory response system to eliminate the threat posed by gram-negative bacteria (endotoxin) and restore health. However, an uncontrolled inflammatory response can lead to tissue damage, organ failure, and ultimately death; this is clinically known as sepsis. Mathematical models of acute inflammatory disease have the potential to guide treatment decisions in critically ill patients. In this work, an 8-state (8-D) differential equation model of the acute inflammatory response system to endotoxin challenge was developed. Endotoxin challenges at 3 and 12 mg/kg were administered to rats, and dynamic cytokine data for interleukin (IL)-6, tumor necrosis factor (TNF), and IL-10 were obtained and used to calibrate the model. Evaluation of competing model structures was performed by analyzing model predictions at 3, 6, and 12 mg/kg endotoxin challenges with respect to experimental data from rats. Subsequently, a model predictive control (MPC) algorithm was synthesized to control a hemoadsorption (HA) device, a blood purification treatment for acute inflammation. A particle filter (PF) algorithm was implemented to estimate the full state vector of the endotoxemic rat based on time series cytokine measurements. Treatment simulations show that: (i) the apparent primary mechanism of HA efficacy is white blood cell (WBC) capture, with cytokine capture a secondary benefit; and (ii) differential filtering of cytokines and WBC does not provide substantial improvement in treatment outcomes vs. existing HA devices.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000391592700005
DO  - DOI:10.3390/pr4040038
UR  - https://juser.fz-juelich.de/record/825974
ER  -