A multiscale model of interleukin-6-mediated immune regulation in Crohn's disease and its application in drug discovery and development.

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-6Rα, o

SUBMITTER: Dwivedi G 

PROVIDER: S-EPMC3910013 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature