Integrated Inflammatory Stress (ITIS) model

Elisabeth Bangsgaard, Poul G. Hjorth, Mette Olufsen, Jesper Mehlsen, Johnny T. Ottesen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review


During the last decade, there has been an increasing interest in the coupling between the acute inflammatory response and the Hypothalamic-Pituitary-Adrenal (HPA) axis. The inflammatory response is activated acutely by pathogen- or damage-related molecular patterns, whereas the HPA axis maintains a long-term level of the stress hormone cortisol which is also anti-inflammatory. A new integrated model of the interaction between these two subsystems of the inflammatory system is proposed and coined the integrated inflammatory stress (ITIS) model. The coupling mechanisms describing the interactions between the subsystems in the ITIS model are formulated based on biological reasoning and its ability to describe clinical data. The ITIS model is calibrated and validated by simulating various scenarios related to endotoxin (LPS) exposure. The model is capable of reproducing human data of tumor necrosis factor alpha, adrenocorticotropic hormone (ACTH) and cortisol and suggests that repeated LPS injections lead to a deficient response. The ITIS model predicts that the most extensive response to an LPS injection in ACTH and cortisol concentrations is observed in the early hours of the day. A constant activation results in elevated levels of the variables in the model while a prolonged change of the oscillations in ACTH and cortisol concentrations is the most pronounced result of different LPS doses predicted by the model.
TidsskriftBulletin of Mathematical Biology
Udgave nummer7
Sider (fra-til)1487-1509
Antal sider22
StatusUdgivet - 2017

Bibliografisk note

Important note from the Publisher regarding the attached version of the article: “This is a post-peer-review, pre-copyedit version of an article published in Bulletin of Mathematical Biology. The final authenticated version is available online at:”.


  • Acute inflammatory system
  • HPA axis
  • Immune system
  • Mathematical modeling
  • Nonlinear ODE model
  • Response to endotoxin (LPS)

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