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Dwivedi2014 - Crohns IL6 Disease model - sgp130 activity

View the 2014-09 Model of the Month entry for this model

Model Identifier
BIOMD0000000536
Short description
Dwivedi2014 - Crohns IL6 Disease model - sgp130 activity
This model is comprised of four models:
Possible avenues for Interleukin-6 (IL-6) inhibition in treating Crohn's disease are compared here. Each model refers to separate ligands. The system simulates differential activity of the ligands on the signalling of IL-6. This affects Signal Transducer and Activator of Transcription 3 (STAT3) activity on the production of biomarker C-Reactive Protein (CRP) expression.
The figure referring to this Crohn's Disease model is 6b.

This model is described in the article:

A multiscale model of interleukin-6-mediated immune regulation in Crohn's disease and its application in drug discovery and development.
Dwivedi G, Fitz L, Hegen M, Martin SW, Harrold J, Heatherington A, Li C.
CPT Pharmacometrics Syst Pharmacol 2014; 3: e89

Abstract:

In this study, we have developed a multiscale systems model of interleukin (IL)-6-mediated immune regulation in Crohn's disease, by integrating intracellular signaling with organ-level dynamics of pharmacological markers underlying the disease. This model was linked to a general pharmacokinetic model for therapeutic monoclonal antibodies and used to comparatively study various biotherapeutic strategies targeting IL-6-mediated signaling in Crohn's disease. Our work illustrates techniques to develop mechanistic models of disease biology to study drug-system interaction. Despite a sparse training data set, predictions of the model were qualitatively validated by clinical biomarker data from a pilot trial with tocilizumab. Model-based analysis suggests that strategies targeting IL-6, IL-6R?, or the IL-6/sIL-6R? complex are less effective at suppressing pharmacological markers of Crohn's than dual targeting the IL-6/sIL-6R? complex in addition to IL-6 or IL-6R?. The potential value of multiscale system pharmacology modeling in drug discovery and development is also discussed.CPT: Pharmacometrics & Systems Pharmacology (2014) 3, e89; doi:10.1038/psp.2013.64; advance online publication 8 January 2014.

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Format
SBML (L2V4)
Related Publication
  • A multiscale model of interleukin-6-mediated immune regulation in Crohn's disease and its application in drug discovery and development.
  • G Dwivedi, L Fitz, M Hegen, S W Martin, J Harrold, A Heatherington, C Li
  • CPT: pharmacometrics & systems pharmacology , 1/ 2014 , Volume 3 , pages: e89 , PubMed ID: 24402116
Contributors
Submitter of the first revision: Vincent Knight-Schrijver
Submitter of this revision: administrator
Curator: Lucian Smith
Modellers: administrator, Vincent Knight-Schrijver

Metadata information

is (2 statements)
BioModels Database BIOMD0000000536
BioModels Database MODEL1408050003

isDescribedBy (1 statement)
PubMed 24402116

hasTaxon (1 statement)
Taxonomy Homo sapiens

hasPart (1 statement)
Gene Ontology JAK-STAT cascade

isVersionOf (1 statement)
hasVersion (1 statement)
Human Disease Ontology Crohn's disease

isPartOf (1 statement)
Curation status
Curated
Modelling approach(es)
ordinary differential equation model

Connected external resources