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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 2019 (8)

Title and authors Publication Year
Cysteinyl leukotriene receptor 2 drives lung immunopathology through a platelet and high mobility box 1-dependent mechanism
T Liu, NA Barrett, Y Kanaoka, K Buchheit, TM Laidlaw, D Garofalo, J Lai, HR Katz, C Feng, JA Boyce
Mucosal Immunology 2019
Margatoxin mitigates CCl4‑induced hepatic fibrosis in mice via macrophage polarization, cytokine secretion and STAT signaling
BM Wu, JD Liu, YH Li, J Li
International journal of molecular medicine 2019
The Role of Mesenchymal Stem Cells in Radiation-Induced Lung Fibrosis
Zanoni, Cortesi, Zamagni, Tesei
International journal of molecular sciences 2019
Concomitant Infection of S. mansoni and H. pylori Promotes Promiscuity of Antigen-Experienced Cells and Primes the Liver for a Lower Fibrotic Response
S Bhattacharjee, R Mejías-Luque, E Loffredo-Verde, A Toska, M Flossdorf, M Gerhard, CP da Costa
Cell Reports 2019
Schistosome infection and its effect on pulmonary circulation
G Butrous
Global Cardiology Science and Practice 2019
Host-directed therapies for parasitic diseases
B Singh, S Varikuti, G Halsey, G Volpedo, OM Hamza, AR Satoskar
Future Medicinal Chemistry 2019
Interaction and involvement of cellular adhesion molecules in the pathogenesis of Schistosomiasis mansoni
VR da Paz, D Figueiredo-Vanzan, A dos Santos Pyrrho
Immunology Letters 2019
Preventive CTLA-4-Ig Treatment Reduces Hepatic Egg Load and Hepatic Fibrosis in Schistosoma mansoni -Infected Mice
M Sombetzki, A Rabes, M Bischofsberger, F Winkelmann, N Koslowski, C Schulz, EC Reisinger
BioMed Research International 2019

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ISSN: 0021-9738 (print), 1558-8238 (online)

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