Inflammatory Bowel Disease: How Effective Is TNF-α Suppression?

PLoS One. 2016 Nov 8;11(11):e0165782. doi: 10.1371/journal.pone.0165782. eCollection 2016.

Abstract

Crohn's Disease (CD) results from inappropriate response toward commensal flora. Earlier studies described CD as a Th1 mediated disease. Current models view both phenotypes as a continuum of various permutations between Th1, Th2 and Th17 pathways compounded by a range of Treg disfunctions. In the present paper, we develop a mathematical model, by a system of differential equations, which describe the dynamic relations among these T cells and their cytokines. The model identities four groups of CD patients according to up/down regulation of Th1 and Th2. The model simulations show that immunosuppression by TNF-α blockage benefits the group with Th1High/Th2Low while, by contrast, the group with Th1Low/Th2High will benefit from immune activation.

MeSH terms

  • Cytokines / physiology
  • Humans
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / immunology
  • Macrophages / physiology
  • Models, Theoretical
  • Th1 Cells / physiology
  • Th17 Cells / physiology
  • Th2 Cells / physiology
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Cytokines
  • Tumor Necrosis Factor-alpha

Grants and funding

This research has been supported by the Mathematical Biosciences Institute and the National Science Foundation under Grant DMS 0931642. WCL was partially supported by a grant from a CityU StUp Grant (No. 7200437). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.