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

• Published in: NPJ systems biology and applications Vol. 10; no. 1; pp. 146 - 11
• Main Authors: Relouw, Freek J. A., Kox, Matthijs, Taal, H. Rob, Koch, Birgit C. P., Prins, Menno W. J., van Riel, Natal A. W.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.12.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/553/1745; 631/553/2700; 631/553/2701; 631/553/2711; Bioinformatics; Biology; Biomedical and Life Sciences; Blood pressure; Computational Biology/Bioinformatics; Computer Appl. in Life Sciences; Computer Simulation; Cytokines; Experiments; Heart rate; Humans; Infections; Inflammation; Intensive care; Laboratory animals; Life Sciences; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Mathematical models; Models, Biological; Ordinary differential equations; Pathophysiology; Sepsis; Sepsis - immunology; Systems Biology; Tumor necrosis factor-TNF
• ISSN: 2056-7189; 2056-7189
• DOI: 10.1038/s41540-024-00473-y

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.