You are viewing a version of a model that has been updated. To access the latest version, and a more detailed display please go here.

Dwivedi2014 - Healthy Volunteer IL6 Model

View the 2014-09 Model of the Month entry for this model
  public model
Short description
Related Publication
  • 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 & systems pharmacology , 0/ 2014 , Volume 3 , pages: e89
  • The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA.
  • 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-6Rα, or the IL-6/sIL-6Rα complex are less effective at suppressing pharmacological markers of Crohn's than dual targeting the IL-6/sIL-6Rα complex in addition to IL-6 or IL-6Rα. 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.
Vincent Knight-Schrijver, administrator

Metadata information

Curation status
Name Description Size Actions

Model files

BIOMD0000000534.xml.origin SBML L2V4 representation of Dwivedi2014 - Healthy Volunteer IL6 Model 183.20 KB Preview | Download

Additional files curation log.txt file summarising all changes made to original model. Includes details of figure reproduction. 1.13 KB Preview | Download

  • Model originally submitted by : Vincent Knight-Schrijver
  • Submitted: Aug 5, 2014 1:41:04 PM
  • Last Modified: Dec 21, 2018 5:27:15 PM
  • Version: 3 public model Download this version
    • Submitted on: Dec 21, 2018 5:27:15 PM
    • Submitted by: administrator
    • With comment: Include the additional files provided by the submitter in the original submission:
  • Version: 2 public model Download this version
    • Submitted on: Nov 4, 2016 2:41:08 PM
    • Submitted by: Vincent Knight-Schrijver
    • With comment: Current version of Dwivedi2014 - Healthy Volunteer IL6 Model
  • Version: 1 public model Download this version
    • Submitted on: Aug 5, 2014 1:41:04 PM
    • Submitted by: Vincent Knight-Schrijver
    • With comment: Original import of Dwivedi2014 - Healthy Volunteer IL6 Model
Curator's comment:
(added: 05 Aug 2014, 17:23:59, updated: 05 Aug 2014, 17:23:59)
Figure 2c: Concentration of serum antibody with monthly (672 hours) dose regimen for three doses, 10 mg, 100 mg and 500 mg. Simulated using a parameter scan for Dose between 10 and 500 with 2 logarithmic intervals. Figure 2d: Concentration of antibody in serum, liver and gut compartments with monthly (672 h) dose regimen. A dose of 100 mg was used. Simulated using a Time Course for 2688 h (16 weeks).