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A physiological model of the inflammatory-thermal-pain-cardiovascular interactions during an endotoxin challenge

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Dobreva, Atanaska ; Brady-Nicholls, Renee ; Larripa, Kamila ; Puelz, Charles ; Mehlsen, Jesper ; Olufsen, Mette S. / A physiological model of the inflammatory-thermal-pain-cardiovascular interactions during an endotoxin challenge. I: The Journal of physiology. 2021 ; Bind 599, Nr. 5. s. 1459-1485.

Bibtex

@article{7bb8f0f7ee47473cbfaf3cfe728c7210,
title = "A physiological model of the inflammatory-thermal-pain-cardiovascular interactions during an endotoxin challenge",
abstract = "KEY POINTS: Inflammation in response to bacterial endotoxin challenge impacts physiological functions, including cardiovascular, thermal and pain dynamics, although the mechanisms are poorly understood. We develop an innovative mathematical model incorporating interaction pathways between inflammation and physiological processes observed in response to an endotoxin challenge. We calibrate the model to individual data from 20 subjects in an experimental study of the human inflammatory and physiological responses to endotoxin, and we validate the model against human data from an independent study. Using the model to simulate patient responses to different treatment modalities reveals that a multimodal treatment combining several therapeutic strategies gives the best recovery outcome.ABSTRACT: Uncontrolled, excessive production of pro-inflammatory mediators from immune cells and traumatized tissues can cause systemic inflammatory conditions such as sepsis, one of the ten leading causes of death in the USA, and one of the three leading causes of death in the intensive care unit. Understanding how inflammation affects physiological processes, including cardiovascular, thermal and pain dynamics, can improve a patient's chance of recovery after an inflammatory event caused by surgery or a severe infection. Although the effects of the autonomic response on the inflammatory system are well-known, knowledge about the reverse interaction is lacking. The present study develops a mathematical model analyzing the inflammatory system's interactions with thermal, pain and cardiovascular dynamics in response to a bacterial endotoxin challenge. We calibrate the model with individual data from an experimental study of the inflammatory and physiological responses to a one-time administration of endotoxin in 20 healthy young men and validate it against data from an independent endotoxin study. We use simulation to explore how various treatments help patients exposed to a sustained pathological input. The treatments explored include bacterial endotoxin adsorption, antipyretics and vasopressors, as well as combinations of these. Our findings suggest that the most favourable recovery outcome is achieved by a multimodal strategy, combining all three interventions to simultaneously remove endotoxin from the body and alleviate symptoms caused by the immune system as it fights the infection.",
keywords = "cardiovascular dynamics, immune response, mathematical modelling, parameter estimation, thermal regulation",
author = "Atanaska Dobreva and Renee Brady-Nicholls and Kamila Larripa and Charles Puelz and Jesper Mehlsen and Olufsen, {Mette S}",
note = "{\textcopyright} 2021 The Authors. The Journal of Physiology {\textcopyright} 2021 The Physiological Society.",
year = "2021",
month = mar,
doi = "10.1113/JP280883",
language = "English",
volume = "599",
pages = "1459--1485",
journal = "The Journal of physiology",
issn = "0022-3751",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "5",

}

RIS

TY - JOUR

T1 - A physiological model of the inflammatory-thermal-pain-cardiovascular interactions during an endotoxin challenge

AU - Dobreva, Atanaska

AU - Brady-Nicholls, Renee

AU - Larripa, Kamila

AU - Puelz, Charles

AU - Mehlsen, Jesper

AU - Olufsen, Mette S

N1 - © 2021 The Authors. The Journal of Physiology © 2021 The Physiological Society.

PY - 2021/3

Y1 - 2021/3

N2 - KEY POINTS: Inflammation in response to bacterial endotoxin challenge impacts physiological functions, including cardiovascular, thermal and pain dynamics, although the mechanisms are poorly understood. We develop an innovative mathematical model incorporating interaction pathways between inflammation and physiological processes observed in response to an endotoxin challenge. We calibrate the model to individual data from 20 subjects in an experimental study of the human inflammatory and physiological responses to endotoxin, and we validate the model against human data from an independent study. Using the model to simulate patient responses to different treatment modalities reveals that a multimodal treatment combining several therapeutic strategies gives the best recovery outcome.ABSTRACT: Uncontrolled, excessive production of pro-inflammatory mediators from immune cells and traumatized tissues can cause systemic inflammatory conditions such as sepsis, one of the ten leading causes of death in the USA, and one of the three leading causes of death in the intensive care unit. Understanding how inflammation affects physiological processes, including cardiovascular, thermal and pain dynamics, can improve a patient's chance of recovery after an inflammatory event caused by surgery or a severe infection. Although the effects of the autonomic response on the inflammatory system are well-known, knowledge about the reverse interaction is lacking. The present study develops a mathematical model analyzing the inflammatory system's interactions with thermal, pain and cardiovascular dynamics in response to a bacterial endotoxin challenge. We calibrate the model with individual data from an experimental study of the inflammatory and physiological responses to a one-time administration of endotoxin in 20 healthy young men and validate it against data from an independent endotoxin study. We use simulation to explore how various treatments help patients exposed to a sustained pathological input. The treatments explored include bacterial endotoxin adsorption, antipyretics and vasopressors, as well as combinations of these. Our findings suggest that the most favourable recovery outcome is achieved by a multimodal strategy, combining all three interventions to simultaneously remove endotoxin from the body and alleviate symptoms caused by the immune system as it fights the infection.

AB - KEY POINTS: Inflammation in response to bacterial endotoxin challenge impacts physiological functions, including cardiovascular, thermal and pain dynamics, although the mechanisms are poorly understood. We develop an innovative mathematical model incorporating interaction pathways between inflammation and physiological processes observed in response to an endotoxin challenge. We calibrate the model to individual data from 20 subjects in an experimental study of the human inflammatory and physiological responses to endotoxin, and we validate the model against human data from an independent study. Using the model to simulate patient responses to different treatment modalities reveals that a multimodal treatment combining several therapeutic strategies gives the best recovery outcome.ABSTRACT: Uncontrolled, excessive production of pro-inflammatory mediators from immune cells and traumatized tissues can cause systemic inflammatory conditions such as sepsis, one of the ten leading causes of death in the USA, and one of the three leading causes of death in the intensive care unit. Understanding how inflammation affects physiological processes, including cardiovascular, thermal and pain dynamics, can improve a patient's chance of recovery after an inflammatory event caused by surgery or a severe infection. Although the effects of the autonomic response on the inflammatory system are well-known, knowledge about the reverse interaction is lacking. The present study develops a mathematical model analyzing the inflammatory system's interactions with thermal, pain and cardiovascular dynamics in response to a bacterial endotoxin challenge. We calibrate the model with individual data from an experimental study of the inflammatory and physiological responses to a one-time administration of endotoxin in 20 healthy young men and validate it against data from an independent endotoxin study. We use simulation to explore how various treatments help patients exposed to a sustained pathological input. The treatments explored include bacterial endotoxin adsorption, antipyretics and vasopressors, as well as combinations of these. Our findings suggest that the most favourable recovery outcome is achieved by a multimodal strategy, combining all three interventions to simultaneously remove endotoxin from the body and alleviate symptoms caused by the immune system as it fights the infection.

KW - cardiovascular dynamics

KW - immune response

KW - mathematical modelling

KW - parameter estimation

KW - thermal regulation

UR - http://www.scopus.com/inward/record.url?scp=85100974826&partnerID=8YFLogxK

U2 - 10.1113/JP280883

DO - 10.1113/JP280883

M3 - Journal article

C2 - 33450068

VL - 599

SP - 1459

EP - 1485

JO - The Journal of physiology

JF - The Journal of physiology

SN - 0022-3751

IS - 5

ER -

ID: 62386571