Mathematical model of chronic pancreatitis

Wenrui Hao; Hannah M. Komar; Phil A. Hart; Darwin L. Conwell; Gregory B. Lesinski; Avner Friedman

doi:10.1073/pnas.1620264114

Mathematical model of chronic pancreatitis

Wenrui Hao, Hannah M. Komar, Phil A. Hart, Darwin L. Conwell, Gregory B. Lesinski, Avner Friedman

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27 Scopus citations

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-α) and tocilizumab or siltuximab (anti-IL-6/IL-6R).

Original language	English
Pages (from-to)	5011-5016
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	114
Issue number	19
DOIs	https://doi.org/10.1073/pnas.1620264114
State	Published - May 9 2017

Bibliographical note

Funding Information:
W.H. and A.F. have been supported by the Mathematical Biosciences Institute and the National Science Foundation under Grant DMS 0931642. This work was also supported in part through funding from the National Institutes of Health, including Grants 1 R01 CA208253-01 (to G.B.L.), 1 R21 AI124687-01 (to G.B.L.), and 1 U01 DK108327-01 (to D.L.C. and P.A.H.) and a grant from Chi Rho Clin, Inc. (to G.B.L.).

Funding

W.H. and A.F. have been supported by the Mathematical Biosciences Institute and the National Science Foundation under Grant DMS 0931642. This work was also supported in part through funding from the National Institutes of Health, including Grants 1 R01 CA208253-01 (to G.B.L.), 1 R21 AI124687-01 (to G.B.L.), and 1 U01 DK108327-01 (to D.L.C. and P.A.H.) and a grant from Chi Rho Clin, Inc. (to G.B.L.).

Funders	Funder number
Chi Rho Clin, Inc.
Mathematical Biosciences Institute
National Science Foundation (NSF)	DMS 0931642
National Institutes of Health (NIH)	1 U01 DK108327-01, 1 R21 AI124687-01
National Childhood Cancer Registry – National Cancer Institute	R01CA208253

Keywords

Chronic pancreatitis
Drug studies
Mathematical model

ASJC Scopus subject areas

General

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10.1073/pnas.1620264114

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title = "Mathematical model of chronic pancreatitis",

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-α) and tocilizumab or siltuximab (anti-IL-6/IL-6R).",

keywords = "Chronic pancreatitis, Drug studies, Mathematical model",

author = "Wenrui Hao and Komar, {Hannah M.} and Hart, {Phil A.} and Conwell, {Darwin L.} and Lesinski, {Gregory B.} and Avner Friedman",

note = "Funding Information: W.H. and A.F. have been supported by the Mathematical Biosciences Institute and the National Science Foundation under Grant DMS 0931642. This work was also supported in part through funding from the National Institutes of Health, including Grants 1 R01 CA208253-01 (to G.B.L.), 1 R21 AI124687-01 (to G.B.L.), and 1 U01 DK108327-01 (to D.L.C. and P.A.H.) and a grant from Chi Rho Clin, Inc. (to G.B.L.).",

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AU - Conwell, Darwin L.

AU - Lesinski, Gregory B.

AU - Friedman, Avner

N1 - Funding Information: W.H. and A.F. have been supported by the Mathematical Biosciences Institute and the National Science Foundation under Grant DMS 0931642. This work was also supported in part through funding from the National Institutes of Health, including Grants 1 R01 CA208253-01 (to G.B.L.), 1 R21 AI124687-01 (to G.B.L.), and 1 U01 DK108327-01 (to D.L.C. and P.A.H.) and a grant from Chi Rho Clin, Inc. (to G.B.L.).

PY - 2017/5/9

Y1 - 2017/5/9

N2 - 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-α) and tocilizumab or siltuximab (anti-IL-6/IL-6R).

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Mathematical model of chronic pancreatitis

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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