An agent-based model of cellular dynamics and circadian variability in human endotoxemia.
As cellular variability and circadian rhythmicity play critical roles in immune and inflammatory responses, we present in this study an agent-based model of human endotoxemia to examine the interplay between circadian controls, cellular variability and stochastic dynamics of inflammatory cytokines....
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3559552?pdf=render |
| _version_ | 1818310360431591424 |
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| author | Tung T Nguyen Steve E Calvano Stephen F Lowry Ioannis P Androulakis |
| author_facet | Tung T Nguyen Steve E Calvano Stephen F Lowry Ioannis P Androulakis |
| author_sort | Tung T Nguyen |
| collection | DOAJ |
| description | As cellular variability and circadian rhythmicity play critical roles in immune and inflammatory responses, we present in this study an agent-based model of human endotoxemia to examine the interplay between circadian controls, cellular variability and stochastic dynamics of inflammatory cytokines. The model is qualitatively validated by its ability to reproduce circadian dynamics of inflammatory mediators and critical inflammatory responses after endotoxin administration in vivo. Novel computational concepts are proposed to characterize the cellular variability and synchronization of inflammatory cytokines in a population of heterogeneous leukocytes. Our results suggest that there is a decrease in cell-to-cell variability of inflammatory cytokines while their synchronization is increased after endotoxin challenge. Model parameters that are responsible for IκB production stimulated by NFκB activation and for the production of anti-inflammatory cytokines have large impacts on system behaviors. Additionally, examining time-dependent systemic responses revealed that the system is least vulnerable to endotoxin in the early morning and most vulnerable around midnight. Although much remains to be explored, proposed computational concepts and the model we have pioneered will provide important insights for future investigations and extensions, especially for single-cell studies to discover how cellular variability contributes to clinical implications. |
| first_indexed | 2024-12-13T07:44:49Z |
| format | Article |
| id | doaj.art-0138dd3945334e7fa779a6814cccdc45 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T07:44:49Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0138dd3945334e7fa779a6814cccdc452022-12-21T23:54:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0181e5555010.1371/journal.pone.0055550An agent-based model of cellular dynamics and circadian variability in human endotoxemia.Tung T NguyenSteve E CalvanoStephen F LowryIoannis P AndroulakisAs cellular variability and circadian rhythmicity play critical roles in immune and inflammatory responses, we present in this study an agent-based model of human endotoxemia to examine the interplay between circadian controls, cellular variability and stochastic dynamics of inflammatory cytokines. The model is qualitatively validated by its ability to reproduce circadian dynamics of inflammatory mediators and critical inflammatory responses after endotoxin administration in vivo. Novel computational concepts are proposed to characterize the cellular variability and synchronization of inflammatory cytokines in a population of heterogeneous leukocytes. Our results suggest that there is a decrease in cell-to-cell variability of inflammatory cytokines while their synchronization is increased after endotoxin challenge. Model parameters that are responsible for IκB production stimulated by NFκB activation and for the production of anti-inflammatory cytokines have large impacts on system behaviors. Additionally, examining time-dependent systemic responses revealed that the system is least vulnerable to endotoxin in the early morning and most vulnerable around midnight. Although much remains to be explored, proposed computational concepts and the model we have pioneered will provide important insights for future investigations and extensions, especially for single-cell studies to discover how cellular variability contributes to clinical implications.http://europepmc.org/articles/PMC3559552?pdf=render |
| spellingShingle | Tung T Nguyen Steve E Calvano Stephen F Lowry Ioannis P Androulakis An agent-based model of cellular dynamics and circadian variability in human endotoxemia. PLoS ONE |
| title | An agent-based model of cellular dynamics and circadian variability in human endotoxemia. |
| title_full | An agent-based model of cellular dynamics and circadian variability in human endotoxemia. |
| title_fullStr | An agent-based model of cellular dynamics and circadian variability in human endotoxemia. |
| title_full_unstemmed | An agent-based model of cellular dynamics and circadian variability in human endotoxemia. |
| title_short | An agent-based model of cellular dynamics and circadian variability in human endotoxemia. |
| title_sort | agent based model of cellular dynamics and circadian variability in human endotoxemia |
| url | http://europepmc.org/articles/PMC3559552?pdf=render |
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