A reduced mathematical model of the acute inflammatory response: I. Derivation of model and analysis of anti-inflammation

Reynolds, Angela; Rubin, Jonathan E.; Clermont, Gilles; Day, Judy; Vodovotz, Yoram; Ermentrout, G. Bard

doi:10.1016/j.jtbi.2006.02.016

Cited by 232 publications

(311 citation statements)

References 31 publications

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“…Many of these defense mechanisms, such as peristalsis and tight junctions between intestinal epithelial cells [1,3,4], are abnormal or decreased in an immature intestine, and thus bacteria normally confined to the intestinal lumen are able to reach systemic organs and tissues. Bacterial translocation triggers the activation of the inflammatory response, which leads to further epithelial damage [3,9]. The inflammatory response is often exaggerated in premature infants due to a lack of differentiation between harmful and beneficial bacteria [1,3].…”

Section: Possible Factors Contributing To Necmentioning

confidence: 99%

Using a mathematical model to analyze the role of probiotics and inflammation in necrotizing enterocolitis

Arciero

Ermentrout

Rubin

et al. 2009

Journal of Critical Care

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Background: Necrotizing enterocolitis (NEC) is a severe disease of the gastrointestinal tract of pre-term babies and is thought to be related to the physiological immaturity of the intestine and altered levels of normal flora in the gut. Understanding the factors that contribute to the pathology of NEC may lead to the development of treatment strategies aimed at re-establishing the integrity of the epithelial wall and preventing the propagation of inflammation in NEC. Several studies have shown a reduced incidence and severity of NEC in neonates treated with probiotics (beneficial bacteria species).

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Section: Possible Factors Contributing To Necmentioning

confidence: 99%

Using a mathematical model to analyze the role of probiotics and inflammation in necrotizing enterocolitis

Arciero

Ermentrout

Rubin

et al. 2009

Journal of Critical Care

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“…A complementary in silico approach has the unique advantage of providing focused and time-efficient integration and analysis of the available literature data, with the capability of generating experimentally testable hypotheses to expedite the investigative process. Although a number of mathematical models recently have been developed and applied to study inflammation (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33), their limited scope and focus predominantly on qualitative representations of inflammation dynamics generally restrict their ability to provide accurate interpretations of existing data sets and generate (semi)quantitative hypotheses. In this article, we introduce a kinetic, inherently quantitative computational model of inflammation whose parameters were derived directly from in vitro data.…”

mentioning

confidence: 99%

Computational Approach To Characterize Causative Factors and Molecular Indicators of Chronic Wound Inflammation

Nagaraja

Wallqvist

Reifman

et al. 2014

The Journal of Immunology

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Chronic inflammation is rapidly becoming recognized as a key contributor to numerous pathologies. Despite detailed investigations, understanding of the molecular mechanisms regulating inflammation is incomplete. Knowledge of such critical regulatory processes and informative indicators of chronic inflammation is necessary for efficacious therapeutic interventions and diagnostic support to clinicians. We used a computational modeling approach to elucidate the critical factors responsible for chronic inflammation and to identify robust molecular indicators of chronic inflammatory conditions. Our kinetic model successfully captured experimentally observed cell and cytokine dynamics for both acute and chronic inflammatory responses. Using sensitivity analysis, we identified macrophage influx and efflux rate modulation as the strongest inducing factor of chronic inflammation for a wide range of scenarios. Moreover, our model predicted that, among all major inflammatory mediators, IL-6, TGF-β, and PDGF may generally be considered the most sensitive and robust indicators of chronic inflammation, which is supported by existing, but limited, experimental evidence.

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“…Two illustrative examples of simple models describing the acute inflammatory response developed for studying and understanding the systemic behavior are presented by Baker et al (2013) and Reynolds et al (2006). The model proposed by Baker et al (2013) is a two-dimensional model classifying all cytokines into proand anti-inflammatory, respectively.…”

Section: Modeling Backgroundmentioning

confidence: 99%

“…This model is analyzed by bifurcation theory in order to investigate the involvement of the pro-and anti-inflammatory cytokines in the disease rheumatoid arthritis (Baker et al 2013). The aim of the work by Reynolds et al (2006) was to investigate the importance of the anti-inflammatory mediators for restoring homeostasis after an infection. This model was developed as a four-dimensional model distinguishing between pathogens, phagocytic cells, a tissue damage marker and antiinflammatory mediators, representing cortisol and IL-10.…”

Section: Modeling Backgroundmentioning

confidence: 99%

“…The elimination of endotoxin is proportional to the product of the number of activated phagocytic cells and the amount of endotoxin (Asachenkov et al 1994;Copeland et al 2005;Harrison et al 2011;Herald 2010;Loosbroock and Hunter 2014;Reynolds et al 2006;Vedder et al 1999;Zuev et al 2006). Thus, there will be no elimination of endotoxin if there is none of the activated phagocytic cells by this modeling choice.…”

Section: Equation For Endotoxin (P)mentioning

confidence: 99%

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Integrated Inflammatory Stress (ITIS) Model

et al. 2017

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Integrated Inflammatory Stress (ITIS) ModelBangsgaard, Elisabeth O.; Hjorth, Poul G.; Olufsen, Mette S.; Mehlsen, Jesper; Ottesen, Johnny T. Published in: Bulletin of Mathematical BiologyLink to article, DOI: 10.1007/s11538-017-0293-2 Publication date: 2017 Document VersionPublisher's PDF, also known as Version of record Abstract During the last decade, there has been an increasing interest in the coupling between the acute inflammatory response and the Hypothalamic-Pituitary-Adrenal (HPA) axis. The inflammatory response is activated acutely by pathogen-or damagerelated molecular patterns, whereas the HPA axis maintains a long-term level of the stress hormone cortisol which is also anti-inflammatory. A new integrated model of the interaction between these two subsystems of the inflammatory system is proposed and coined the integrated inflammatory stress (ITIS) model. The coupling mechanisms describing the interactions between the subsystems in the ITIS model are formulated based on biological reasoning and its ability to describe clinical data. The ITIS model is calibrated and validated by simulating various scenarios related to endotoxin (LPS) exposure. The model is capable of reproducing human data of tumor necrosis factor alpha, adrenocorticotropic hormone (ACTH) and cortisol and suggests that repeated LPS injections lead to a deficient response. The ITIS model predicts that the most extensive response to an LPS injection in ACTH and cortisol concentrations is observed in the early hours of the day. A constant activation results in elevated levels of the variables in the model while a prolonged change of the oscillations in ACTH and

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A reduced mathematical model of the acute inflammatory response: I. Derivation of model and analysis of anti-inflammation

Cited by 232 publications

References 31 publications

Using a mathematical model to analyze the role of probiotics and inflammation in necrotizing enterocolitis

Using a mathematical model to analyze the role of probiotics and inflammation in necrotizing enterocolitis

Computational Approach To Characterize Causative Factors and Molecular Indicators of Chronic Wound Inflammation

Integrated Inflammatory Stress (ITIS) Model

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