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 -