A Asachenkov

A Beishuizen

A Reynolds

AM Madsen

C Loosbroock

CA Dinarello

CC Chow

CD John

DG Harrison

Elisabeth O. Bangsgaard

EM Sternberg

EO Bangsgaard

ESV Amersfoort

G Clermont

G Nieman

H Malek

H Vedder

J Day

J Rankin

J Scheller

Jesper Mehlsen

JI Webster

JJ Walker

JM Cavaillon

Johnny T. Ottesen

KJ Tracey

M Baker

M Bianchi

M Clodi

M Conrad

M Meyer-Hermann

MC Herald

Mette S. Olufsen

MN Silverman

MP Yeager

P Liakos

Poul G. Hjorth

S Copeland

S Gupta

S Jelić

S Sanjabi

SM Opal

SM Zuev

U Albrecht

English

During the last decade, there has been an increasing interest in the coupling between the acute inflammatory response and the Hypothalamicâ€“Pituitaryâ€“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

Bangsgaard, Elisabeth O.

Hjorth, Poul G.

Olufsen, Mette S.

Mehlsen, Jesper

Ottesen, Johnny T.

Online Research Database In Technology

Integrated Inflammatory Stress (ITIS) Model

Crossref

Bulletin of Mathematical Biology

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.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

Bangsgaard, Elisabeth

Olufsen, Mette

Roskilde Universitet

Integrated Inflammatory Stress (ITIS) model

http://orbit.dtu.dk/ws/files/134063399/filestore_4_.pdf

Integrated Inflammatory Stress (ITIS) model

Abstract

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Online Research Database In Technology

Crossref

Roskilde Universitet