title: Translational applications of evaluating physiologic variability in human endotoxemia.
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.
authors.affiliation: Department of Biomedical Engineering, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Scheff
authors.forename: Panteleimon D
authors.initials: PD
authors.lastname: Mavroudis
authors.forename: Steve E
authors.initials: SE
authors.lastname: Calvano
authors.forename: Ioannis P
authors.initials: IP
authors.lastname: Androulakis
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000503:physiopathology; D002940:Circadian Rhythm; D019446:Endotoxemia / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology; D006706:Homeostasis; D006728:Hormones / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007249:Inflammation; D008070:Lipopolysaccharides / Q000737:chemistry; D008962:Models, Theoretical; D018805:Sepsis / Q000503:physiopathology; D013997:Time Factors; D014158:Transcription, Genetic; D057170:Translational Research, Biomedical / Q000379:methods
chemical_list: D006728:Hormones; D008070:Lipopolysaccharides; D006854:Hydrocortisone