Mathematical model of chronic pancreatitis

Proc Natl Acad Sci U S A. 2017 May 9;114(19):5011-5016. doi: 10.1073/pnas.1620264114. Epub 2017 Apr 24.

Abstract

Chronic pancreatitis (CP) is a progressive inflammatory disease of the pancreas, leading to its fibrotic destruction. There are currently no drugs that can stop or slow the progression of the disease. The etiology of the disease is multifactorial, whereas recurrent attacks of acute pancreatitis are thought to precede the development of CP. A better understanding of the pathology of CP is needed to facilitate improved diagnosis and treatment strategies for this disease. The present paper develops a mathematical model of CP based on a dynamic network that includes macrophages, pancreatic stellate cells, and prominent cytokines that are present at high levels in the CP microenvironment. The model is represented by a system of partial differential equations. The model is used to explore in silico potential drugs that could slow the progression of the disease, for example infliximab (anti-TNF-[Formula: see text]) and tocilizumab or siltuximab (anti-IL-6/IL-6R).

Keywords: chronic pancreatitis; drug studies; mathematical model.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Fibrosis
  • Humans
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / metabolism
  • Models, Biological*
  • Pancreas / metabolism*
  • Pancreas / pathology
  • Pancreatitis, Chronic / drug therapy
  • Pancreatitis, Chronic / metabolism*
  • Pancreatitis, Chronic / pathology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • IL6 protein, human
  • Interleukin-6
  • Tumor Necrosis Factor-alpha