A Kinetic Response Model for Standardized Regression Analyses of Inflammation-Triggered Hypothermic Body Temperature-Time Courses in Mice.

Autor: Diebner HH; Department of Medical Informatics, Biometry and Epidemiology, Ruhr-Universität Bochum, Bochum, Germany., Reinke S; Department of Pediatrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Rösen-Wolff A; Department of Pediatrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany., Winkler S; Department of Pediatrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Jazyk: angličtina
Zdroj: Frontiers in physiology [Front Physiol] 2021 Aug 24; Vol. 12, pp. 634510. Date of Electronic Publication: 2021 Aug 24 (Print Publication: 2021).
DOI: 10.3389/fphys.2021.634510
Abstrakt: LPS is frequently used to induce experimental endotoxic shock, representing a standard model of acute inflammation in mice. The resulting inflammatory response leads to hypothermia of the experimental animals, which in turn can be used as surrogate for the severity of systemic inflammation. Although increasingly applied as a humane endpoint in murine studies, differences between obtained temperature-time curves are typically evaluated at a single time point with t -tests or ANOVA analyses. We hypothesized that analyses of the entire temperature-time curves using a kinetic response model could fit the data, which show a temperature decrease followed by a tendency to return to normal temperature, and could increase the statistical power. Using temperature-time curves obtained from LPS stimulated mice, we derived a biologically motivated kinetic response model based on a differential equation. The kinetic model includes four parameters: (i) normal body temperature ( T n ), (ii) a coefficient related to the force of temperature autoregulation ( r ), (iii) damage strength ( p 0 ), and (iv) clearance rate ( k ). Kinetic modeling of temperature-time curves obtained from LPS stimulated mice is feasible and leads to a high goodness-of-fit. Here, modifying key enzymes of inflammatory cascades induced a dominant impact of genotypes on the damage strength and a weak impact on the clearance rate. Using a likelihood-ratio test to compare modeled curves of different experimental groups yields strongly enhanced statistical power compared to pairwise t -tests of single temperature time points. Taken together, the kinetic model presented in this study has several advantages compared to simple analysis of individual time points and therefore may be used as a standard method for assessing inflammation-triggered hypothermic response curves in mice.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Diebner, Reinke, Rösen-Wolff and Winkler.)
Databáze: MEDLINE
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