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Citations to this article

An IL-13 inhibitor blocks the development of hepatic fibrosis during a T-helper type 2–dominated inflammatory response
Mónica G. Chiaramonte, … , Allen W. Cheever, Thomas A. Wynn
Mónica G. Chiaramonte, … , Allen W. Cheever, Thomas A. Wynn
Published September 15, 1999
Citation Information: J Clin Invest. 1999;104(6):777-785. https://doi.org/10.1172/JCI7325.
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An IL-13 inhibitor blocks the development of hepatic fibrosis during a T-helper type 2–dominated inflammatory response

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Abstract

In schistosomiasis, chronic parasite egg–induced granuloma formation can lead to tissue destruction and fibrosis, which causes much of the morbidity and mortality associated with this disease. Here we show the importance of IL-13 in the pathogenesis of schistosomiasis, and demonstrate, perhaps for the first time, the therapeutic efficacy of an IL-13 inhibitor, sIL-13Rα2-Fc, in the control of hepatic fibrosis. T-helper type 2 (Th2) cytokines dominate the immune response in mice infected with Schistosoma mansoni, yet the specific contributions of IL-13 and IL-4 to the development of fibrosis were not previously investigated. Our studies demonstrate that both cytokines play redundant roles in granuloma formation, which explains the ability of IL-4–deficient mice to form granulomas around eggs. More importantly, however, these studies demonstrate that IL-13 is the dominant Th2-type cytokine regulating fibrosis. IL-13 stimulated collagen production in fibroblasts, and procollagen I and procollagen III mRNA expression was decreased in sIL-13Rα2-Fc–treated mice. Moreover, the reduction in fibrosis observed in IL-4–deficient mice was much less pronounced than that in sIL-13Rα2-Fc–treated animals. Fibrosis is a major pathological manifestation of a number of allergic, autoimmune, and infectious diseases. Thus, our findings provide evidence that IL-13 inhibitors may be of general therapeutic benefit in preventing damaging tissue fibrosis resulting from Th2-dominated inflammatory responses.

Authors

Mónica G. Chiaramonte, Debra D. Donaldson, Allen W. Cheever, Thomas A. Wynn

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 Total
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Citations to this article in year 2008 (20)

Title and authors Publication Year
Cellular and molecular mechanisms of fibrosis
TA Wynn
The Journal of Pathology 2008
Cationic amino acid transporter-2 regulates immunity by modulating arginase activity
RW Thompson, JT Pesce, T Ramalingam, MS Wilson, S White, AW Cheever, SM Ricklefs, SF Porcella, L Li, LG Ellies, TA Wynn
PLoS pathogens 2008
Immune Interactions in Hepatic Fibrosis
AP Holt, M Salmon, CD Buckley, DH Adams
Clinics in Liver Disease 2008
Coinfection with the Intestinal Nematode Heligmosomoides polygyrus Markedly Reduces Hepatic Egg-Induced Immunopathology and Proinflammatory Cytokines in Mouse Models of Severe Schistosomiasis
LE Bazzone, PM Smith, LI Rutitzky, MG Shainheit, JF Urban, T Setiawan, AM Blum, JV Weinstock, MJ Stadecker
Infection and immunity 2008
T cells, B cells, and polarized immune response in the pathogenesis of fibrosis and systemic sclerosis
C Chizzolini
Current Opinion in Rheumatology 2008
Transgenic Expression of Interleukin-13 in the Skin Induces a Pruritic Dermatitis and Skin Remodeling
T Zheng, MH Oh, SY Oh, JT Schroeder, AB Glick, Z Zhu
Journal of Investigative Dermatology 2008
Advances in antifibrotic therapy
Z Ghiassi-Nejad, SL Friedman
Expert Review of Gastroenterology & Hepatology 2008
Regulatory role of interleukin-10 and interferon-gamma in severe hepatic central and peripheral fibrosis in humans infected with Schistosoma japonicum
V Arnaud, J Li, Y Wang, X Fu, S Mengzhi, X Luo, X Hou, H Dessein, Z Jie, Y Xin-Ling, H He, DP McManus, Y Li, A Dessein
The Journal of Infectious Diseases 2008
A novel and sensitive ELISA reveals that the soluble form of IL-13R-alpha2 is not expressed in plasma of healthy or asthmatic subjects
M O'Toole, H Legault, R Ramsey, TA Wynn, MT Kasaian
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 2008
Role of the Transcriptional Repressor BCL6 in Allergic Response and Inflammation
M Arima, T Fukuda, T Tokuhisa
World Allergy Organization Journal 2008
Interleukin-13 exerts autocrine growth-promoting effects on human pancreatic cancer, and its expression correlates with a propensity for lymph node metastases
A Formentini, O Prokopchuk, J Sträter, J Kleeff, LF Grochola, G Leder, D Henne-Bruns, M Korc, M Kornmann
International Journal of Colorectal Disease 2008
Immune response and pathogenesis of neuroschistosomiasis mansoni
TC Ferrari, G Gazzinelli, R Corrêa-Oliveira
Acta Tropica 2008
Eosinophil activation status, cytokines and liver fibrosis in Schistosoma mansoni infected patients
D Silveira-Lemos, A Teixeira-Carvalho, OA Martins-Filho, LF Oliveira, MF Costa-Silva, LF Matoso, LJ de Souza, A Gazzinelli, R Corrêa-Oliveira
Acta Tropica 2008
Transforming Growth Factor-β Regulates House Dust Mite–induced Allergic Airway Inflammation but Not Airway Remodeling
R Fattouh, NG Midence, K Arias, JR Johnson, TD Walker, S Goncharova, KP Souza, RC Gregory, S Lonning, J Gauldie, M Jordana
American journal of respiratory and critical care medicine 2008
Cationic Amino Acid Transporter-2 Regulates Immunity by Modulating Arginase Activity
RW Thompson, JT Pesce, T Ramalingam, MS Wilson, S White, AW Cheever, SM Ricklefs, SF Porcella, L Li, LG Ellies, TA Wynn, EJ Pearce
PLoS pathogens 2008
Cytokine profile associated with chronic and acute human schistosomiasis mansoni
CN de Morais, JR de Souza, WG Melo, ML Aroucha, P Miranda, AL Domingues, FG Abath, SM Montenegro
Memórias do Instituto Oswaldo Cruz 2008
The IL-4Rα pathway in macrophages and its potential role in silica-induced pulmonary fibrosis
CT Migliaccio, MC Buford, F Jessop, A Holian
Journal of leukocyte biology 2008
Murine gammaherpesvirus-induced fibrosis is associated with the development of alternatively activated macrophages
B Gangadharan, MA Hoeve, JE Allen, B Ebrahimi, SM Rhind, BM Dutia, AA Nash
Journal of leukocyte biology 2008
Mechanisms of Oncostatin M-Induced Pulmonary Inflammation and Fibrosis
A Mozaffarian, AW Brewer, ES Trueblood, IG Luzina, NW Todd, SP Atamas, HA Arnett
Journal of immunology (Baltimore, Md. : 1950) 2008
IL-4Rα Expression by Bone Marrow-Derived Cells Is Necessary and Sufficient for Host Protection against Acute Schistosomiasis
DB Herbert, T Orekov, C Perkins, ME Rothenberg, FD Finkelman
Journal of immunology (Baltimore, Md. : 1950) 2008

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