Mathematical model of the inflammatory response to acute and prolonged lipopolysaccharide exposure in humans

Freek J A Relouw; Matthijs Kox; H Rob Taal; Birgit C P Koch; Menno W J Prins; Natal A W van Riel

doi:10.1038/s41540-024-00473-y

Mathematical model of the inflammatory response to acute and prolonged lipopolysaccharide exposure in humans

NPJ Syst Biol Appl. 2024 Dec 5;10(1):146. doi: 10.1038/s41540-024-00473-y.

Authors

Freek J A Relouw^{1

2

3

4

5}, Matthijs Kox⁶, H Rob Taal⁷, Birgit C P Koch⁸, Menno W J Prins^{9

10

11}, Natal A W van Riel^{12

13}

Affiliations

¹ Department of Intensive Care Medicine, Radboud university medical center, Nijmegen, The Netherlands. [email protected].
² Department of Neonatal and Paediatric Intensive Care, Division of Neonatology, Erasmus University Medical Center, Rotterdam, The Netherlands. [email protected].
³ Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands. [email protected].
⁴ Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands. [email protected].
⁵ Institute of Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands. [email protected].
⁶ Department of Intensive Care Medicine, Radboud university medical center, Nijmegen, The Netherlands.
⁷ Department of Neonatal and Paediatric Intensive Care, Division of Neonatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁸ Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁹ Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
¹⁰ Institute of Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands.
¹¹ Department of Applied Physics, Eindhoven University of Technology, Eindhoven, The Netherlands.
¹² Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands. [email protected].
¹³ Institute of Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands. [email protected].

Abstract

One in five deaths worldwide is associated with sepsis, which is defined as organ dysfunction caused by a dysregulated host response to infection. An increased understanding of the pathophysiology of sepsis could provide improved approaches for early detection and treatment. Here we describe the development and validation of a mechanistic mathematical model of the inflammatory response, making use of a combination of in vitro and human in vivo data obtained from experiments where bacterial lipopolysaccharide (LPS) was used to induce an inflammatory response. The new model can simulate the responses to both acute and prolonged inflammatory stimuli in an experimental setting, as well as the response to infection in the clinical setting. This model serves as a foundation for a sepsis simulation model with a potentially wide range of applications in different disciplines involved with sepsis research.

MeSH terms

Computer Simulation
Humans
Inflammation*
Lipopolysaccharides* / pharmacology
Models, Biological
Sepsis* / immunology

Substances

Lipopolysaccharides