The Resolution of Inflammation: A Mathematical Model of Neutrophil and Macrophage Interactions

Handle URI:
http://hdl.handle.net/10754/599951
Title:
The Resolution of Inflammation: A Mathematical Model of Neutrophil and Macrophage Interactions
Authors:
Dunster, J. L.; Byrne, H. M.; King, J. R.
Abstract:
© 2014, Society for Mathematical Biology. There is growing interest in inflammation due to its involvement in many diverse medical conditions, including Alzheimer’s disease, cancer, arthritis and asthma. The traditional view that resolution of inflammation is a passive process is now being superceded by an alternative hypothesis whereby its resolution is an active, anti-inflammatory process that can be manipulated therapeutically. This shift in mindset has stimulated a resurgence of interest in the biological mechanisms by which inflammation resolves. The anti-inflammatory processes central to the resolution of inflammation revolve around macrophages and are closely related to pro-inflammatory processes mediated by neutrophils and their ability to damage healthy tissue. We develop a spatially averaged model of inflammation centring on its resolution, accounting for populations of neutrophils and macrophages and incorporating both pro- and anti-inflammatory processes. Our ordinary differential equation model exhibits two outcomes that we relate to healthy and unhealthy states. We use bifurcation analysis to investigate how variation in the system parameters affects its outcome. We find that therapeutic manipulation of the rate of macrophage phagocytosis can aid in resolving inflammation but success is critically dependent on the rate of neutrophil apoptosis. Indeed our model predicts that an effective treatment protocol would take a dual approach, targeting macrophage phagocytosis alongside neutrophil apoptosis.
Citation:
Dunster JL, Byrne HM, King JR (2014) The Resolution of Inflammation: A Mathematical Model of Neutrophil and Macrophage Interactions. Bull Math Biol 76: 1953–1980. Available: http://dx.doi.org/10.1007/s11538-014-9987-x.
Publisher:
Springer Science + Business Media
Journal:
Bulletin of Mathematical Biology
KAUST Grant Number:
KUK-013-04
Issue Date:
23-Jul-2014
DOI:
10.1007/s11538-014-9987-x
PubMed ID:
25053556
Type:
Article
ISSN:
0092-8240; 1522-9602
Sponsors:
JLD gratefully acknowledges support from the Engineering and Physical Sciences Research Council, the Health and Safety Laboratory and the industrial mathematics KTN for this work in the form of a CASE studentship. JRK acknowledges the funding of the Royal Society and Wolfson Foundation. The work of HMB was supported in part by Award No. KUK-013-04, made by King Abdullah University of Science and Technology (KAUST).
Appears in Collections:
Publications Acknowledging KAUST Support

Full metadata record

DC FieldValue Language
dc.contributor.authorDunster, J. L.en
dc.contributor.authorByrne, H. M.en
dc.contributor.authorKing, J. R.en
dc.date.accessioned2016-02-28T06:33:07Zen
dc.date.available2016-02-28T06:33:07Zen
dc.date.issued2014-07-23en
dc.identifier.citationDunster JL, Byrne HM, King JR (2014) The Resolution of Inflammation: A Mathematical Model of Neutrophil and Macrophage Interactions. Bull Math Biol 76: 1953–1980. Available: http://dx.doi.org/10.1007/s11538-014-9987-x.en
dc.identifier.issn0092-8240en
dc.identifier.issn1522-9602en
dc.identifier.pmid25053556en
dc.identifier.doi10.1007/s11538-014-9987-xen
dc.identifier.urihttp://hdl.handle.net/10754/599951en
dc.description.abstract© 2014, Society for Mathematical Biology. There is growing interest in inflammation due to its involvement in many diverse medical conditions, including Alzheimer’s disease, cancer, arthritis and asthma. The traditional view that resolution of inflammation is a passive process is now being superceded by an alternative hypothesis whereby its resolution is an active, anti-inflammatory process that can be manipulated therapeutically. This shift in mindset has stimulated a resurgence of interest in the biological mechanisms by which inflammation resolves. The anti-inflammatory processes central to the resolution of inflammation revolve around macrophages and are closely related to pro-inflammatory processes mediated by neutrophils and their ability to damage healthy tissue. We develop a spatially averaged model of inflammation centring on its resolution, accounting for populations of neutrophils and macrophages and incorporating both pro- and anti-inflammatory processes. Our ordinary differential equation model exhibits two outcomes that we relate to healthy and unhealthy states. We use bifurcation analysis to investigate how variation in the system parameters affects its outcome. We find that therapeutic manipulation of the rate of macrophage phagocytosis can aid in resolving inflammation but success is critically dependent on the rate of neutrophil apoptosis. Indeed our model predicts that an effective treatment protocol would take a dual approach, targeting macrophage phagocytosis alongside neutrophil apoptosis.en
dc.description.sponsorshipJLD gratefully acknowledges support from the Engineering and Physical Sciences Research Council, the Health and Safety Laboratory and the industrial mathematics KTN for this work in the form of a CASE studentship. JRK acknowledges the funding of the Royal Society and Wolfson Foundation. The work of HMB was supported in part by Award No. KUK-013-04, made by King Abdullah University of Science and Technology (KAUST).en
dc.publisherSpringer Science + Business Mediaen
dc.subjectBifurcation analysisen
dc.subjectInflammationen
dc.subjectMathematical modellingen
dc.subjectResolutionen
dc.titleThe Resolution of Inflammation: A Mathematical Model of Neutrophil and Macrophage Interactionsen
dc.typeArticleen
dc.identifier.journalBulletin of Mathematical Biologyen
dc.contributor.institutionUniversity of Reading, Reading, United Kingdomen
dc.contributor.institutionUniversity of Oxford, Oxford, United Kingdomen
dc.contributor.institutionComputational Biology Group, Oxford, United Kingdomen
dc.contributor.institutionUniversity of Nottingham, Nottingham, United Kingdomen
kaust.grant.numberKUK-013-04en
All Items in KAUST are protected by copyright, with all rights reserved, unless otherwise indicated.