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A multiscale modeling approach to inflammation: A case study in human endotoxemia

Scheff, Jeremy D. and Mavroudis, Panteleimon D. and Foteinou, Panagiota T. and An, Gary and Calvano, Steve E. and Doyle, John and Dick, Thomas E. and Lowry, Stephen F. and Vodovotz, Yoram and Androulakis, Ioannis P. (2013) A multiscale modeling approach to inflammation: A case study in human endotoxemia. Journal of Computational Physics, 244 . pp. 279-289. ISSN 0021-9991.

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Inflammation is a critical component in the body’s response to injury. A dysregulated inflammatory response, in which either the injury is not repaired or the inflammatory response does not appropriately self-regulate and end, is associated with a wide range of inflammatory diseases such as sepsis. Clinical management of sepsis is a significant problem, but progress in this area has been slow. This may be due to the inherent nonlinearities and complexities in the interacting multiscale pathways that are activated in response to systemic inflammation, motivating the application of systems biology techniques to better understand the inflammatory response. Here, we review our past work on a multiscale modeling approach applied to human endotoxemia, a model of systemic inflammation, consisting of a system of compartmentalized differential equations operating at different time scales and through a discrete model linking inflammatory mediators with changing patterns in the beating of the heart, which has been correlated with outcome and severity of inflammatory disease despite unclear mechanistic underpinnings. Working towards unraveling the relationship between inflammation and heart rate variability (HRV) may enable greater understanding of clinical observations as well as novel therapeutic targets.

Item Type:Article
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Doyle, John0000-0002-1828-2486
Additional Information:© 2012 Published by Elsevier Inc. Available online 29 September 2012. JDS, PDM, SEC and SFL are supported, in part, from NIH GM34695. PDM and IPA acknowledge support from NIH GM082974. This work was supported in part by the National Institutes of Health Grants R01GM67240, P50GM53789, R33HL089082, UO1 DK072146-05, R01HL080926, R01AI080799, R01HL76157, 3R01GM034695-25S1, and R01GM082974; National Institute on Disability and Rehabilitation Research Grant H133E070024; as well as grants from the Commonwealth of Pennsylvania, the Pittsburgh Lifesciences Greenhouse, and the Pittsburgh Tissue Engineering Initiative.
Funding AgencyGrant Number
NIHUO1 DK072146-05
National Institute on Disability and Rehabilitation ResearchH133E070024
Commonwealth of PennsylvaniaUNSPECIFIED
Pittsburgh Lifesciences GreenhouseUNSPECIFIED
Pittsburgh Tissue Engineering InitiativeUNSPECIFIED
Subject Keywords:Systems biology; Heart rate variability; Circadian; Microarray; Autonomic dysfunction
Record Number:CaltechAUTHORS:20130628-075744899
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Official Citation:Jeremy D. Scheff, Panteleimon D. Mavroudis, Panagiota T. Foteinou, Gary An, Steve E. Calvano, John Doyle, Thomas E. Dick, Stephen F. Lowry, Yoram Vodovotz, Ioannis P. Androulakis, A multiscale modeling approach to inflammation: A case study in human endotoxemia, Journal of Computational Physics, Volume 244, 1 July 2013, Pages 279-289, ISSN 0021-9991,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:39132
Deposited By: Tony Diaz
Deposited On:28 Jun 2013 16:05
Last Modified:26 Nov 2019 11:15

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