Translational applications of evaluating physiologic variability in human endotoxemia

J Clin Monit Comput. 2013 Aug;27(4):405-15. doi: 10.1007/s10877-012-9418-1. Epub 2012 Dec 1.

Abstract

Dysregulation of the inflammatory response is a critical component of many clinically challenging disorders such as sepsis. Inflammation is a biological process designed to lead to healing and recovery, ultimately restoring homeostasis; however, the failure to fully achieve those beneficial results can leave a patient in a dangerous persistent inflammatory state. One of the primary challenges in developing novel therapies in this area is that inflammation is comprised of a complex network of interacting pathways. Here, we discuss our approaches towards addressing this problem through computational systems biology, with a particular focus on how the presence of biological rhythms and the disruption of these rhythms in inflammation may be applied in a translational context. By leveraging the information content embedded in physiologic variability, ranging in scale from oscillations in autonomic activity driving short-term heart rate variability to circadian rhythms in immunomodulatory hormones, there is significant potential to gain insight into the underlying physiology.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Autonomic Nervous System / physiopathology
  • Circadian Rhythm
  • Endotoxemia / physiopathology*
  • Heart Rate / physiology
  • Homeostasis
  • Hormones / metabolism
  • Humans
  • Hydrocortisone / metabolism
  • Inflammation
  • Lipopolysaccharides / chemistry
  • Models, Theoretical
  • Sepsis / physiopathology
  • Time Factors
  • Transcription, Genetic
  • Translational Medical Research / methods

Substances

  • Hormones
  • Lipopolysaccharides
  • Hydrocortisone