Integrated Inflammatory Stress (ITIS) model

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.
OriginalsprogEngelsk
TidsskriftBulletin of Mathematical Biology
Vol/bind79
Udgave nummer7
Sider (fra-til)1487-1509
Antal sider22
ISSN0092-8240
DOI
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: http://dx.doi.org/10.1007/s11538-017-0293-2”.

Emneord

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

Citer dette

Bangsgaard, Elisabeth ; Hjorth, Poul G. ; Olufsen, Mette ; Mehlsen, Jesper ; Ottesen, Johnny T. / Integrated Inflammatory Stress (ITIS) model. I: Bulletin of Mathematical Biology. 2017 ; Bind 79, Nr. 7. s. 1487-1509.
@article{1a55499f34624f5a924a84f69b60a075,
title = "Integrated Inflammatory Stress (ITIS) model",
abstract = "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.",
keywords = "Acute inflammatory system, HPA axis, Immune system, Mathematical modeling, Nonlinear ODE model, Response to endotoxin (LPS), Acute inflammatory system, HPA axis, Immune system, Mathematical modeling, Nonlinear ODE model, Response to endotoxin (LPS)",
author = "Elisabeth Bangsgaard and Hjorth, {Poul G.} and Mette Olufsen and Jesper Mehlsen and Ottesen, {Johnny T.}",
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: http://dx.doi.org/10.1007/s11538-017-0293-2”.",
year = "2017",
doi = "10.1007/s11538-017-0293-2",
language = "English",
volume = "79",
pages = "1487--1509",
journal = "Bulletin of Mathematical Biology",
issn = "0092-8240",
publisher = "Springer New York LLC",
number = "7",

}

Bangsgaard, E, Hjorth, PG, Olufsen, M, Mehlsen, J & Ottesen, JT 2017, 'Integrated Inflammatory Stress (ITIS) model', Bulletin of Mathematical Biology, bind 79, nr. 7, s. 1487-1509. https://doi.org/10.1007/s11538-017-0293-2

Integrated Inflammatory Stress (ITIS) model. / Bangsgaard, Elisabeth; Hjorth, Poul G.; Olufsen, Mette; Mehlsen, Jesper; Ottesen, Johnny T.

I: Bulletin of Mathematical Biology, Bind 79, Nr. 7, 2017, s. 1487-1509.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Integrated Inflammatory Stress (ITIS) model

AU - Bangsgaard, Elisabeth

AU - Hjorth, Poul G.

AU - Olufsen, Mette

AU - Mehlsen, Jesper

AU - Ottesen, Johnny T.

N1 - 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: http://dx.doi.org/10.1007/s11538-017-0293-2”.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Acute inflammatory system

KW - HPA axis

KW - Immune system

KW - Mathematical modeling

KW - Nonlinear ODE model

KW - Response to endotoxin (LPS)

KW - Acute inflammatory system

KW - HPA axis

KW - Immune system

KW - Mathematical modeling

KW - Nonlinear ODE model

KW - Response to endotoxin (LPS)

U2 - 10.1007/s11538-017-0293-2

DO - 10.1007/s11538-017-0293-2

M3 - Journal article

VL - 79

SP - 1487

EP - 1509

JO - Bulletin of Mathematical Biology

JF - Bulletin of Mathematical Biology

SN - 0092-8240

IS - 7

ER -