Using Agent-Based Modeling to Study Interstitial Lung Disease

Using Agent-Based Modeling to Study Interstitial Lung Disease

Virginia A. Folcik 1, Gerard Nuovo 2,1, Samir N. Ghadiali 3,1, James N. Allen1 and Clay B. Marsh 1,4

1 Department of Internal Medicine, Division of Pulmonary Allergy Critical Care and Sleep Medicine, The Ohio State University 2Department of Pathology, The Ohio State University 3Department of Biomedical Engineering, The Ohio State University 4Departments of Medicine Administration, Health Sciences Administration, Molecular Virology, Immunology and Medical Genetics and Veterinary Biosciences, The Ohio State University

The Basic Immune Simulator (http://www.tbiomed.com/content/4/1/39) is an agent-based model that was created using Repast to model the immune system as a complex system and to study inflammation and disease. Agents in this model represent cells and other structural components. Signals in this model represent cytokines, chemokines and other mediators released by cells. The simulator is programmed to model many different disease processes, including viral or bacterial infection, cancer, transplant rejection and a response to injury (i.e. wound healing). It can also be used to test virtual intervention in any of these processes. The Basic Immune Simulator has been updated to include a more complete set of lymphocytes, more detailed innate immune system behavior and it has been adapted to model lung tissue. This is an example of how the modularity of the original model can be exploited to model a specific tissue and disease. While the basic components of the immune system present in individuals remain relatively constant during adulthood, the behavior of the cells of immune system changes depending upon their local environment and the health status of the individual. In the absence of perturbation, the cells remain in a steady state, some carrying out “housekeeping” tasks, such as the macrophages scavenging debris in the lung. The immune system can also underlie advanced lung diseases, such as “Interstitial Lung Diseases”. In these diseases, lung function is impaired by the overgrowth (fibrosis) or destruction of the tissue involved in gas exchange. Although the pathogenesis is not known, experts speculate that aberrant wound repair of the lung may be involved. A minority of cases are hereditary. The goal of this modeling work is to determine what cellular behavior(s) have the highest probability of being the underlying abnormalities in the cause and response to treatment of pulmonary fibrosis. The results will provide direction to diagnose, treat and follow patients with this disease.

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