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

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

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)279-289
Number of pages11
JournalJournal of Computational Physics
Volume244
DOIs
StatePublished - Jul 1 2013

All Science Journal Classification (ASJC) codes

  • Numerical Analysis
  • Modeling and Simulation
  • Physics and Astronomy (miscellaneous)
  • General Physics and Astronomy
  • Computer Science Applications
  • Computational Mathematics
  • Applied Mathematics

Keywords

  • Autonomic dysfunction
  • Circadian
  • Heart rate variability
  • Microarray
  • Systems biology

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