Regulation of pathogenic IL-17 responses in collagen-induced arthritis: roles of endogenous interferon-gamma and IL-4

Persistent Link:
http://hdl.handle.net/10150/610381
Title:
Regulation of pathogenic IL-17 responses in collagen-induced arthritis: roles of endogenous interferon-gamma and IL-4
Author:
Sarkar, Sujata; Cooney, Laura; White, Peter; Dunlop, Deborah; Endres, Judith; Jorns, Julie; Wasco, Matthew; Fox, David
Affiliation:
Section of Rheumatology, Department of Medicine, University of Arizona, 1501 N. Campbell Avenue, Rm 6310, Tucson, Arizona 85724, USA; Division of Rheumatology, Department of Internal Medicine, and Rheumatic Disease Core Center, University of Michigan, 1500 E Medical Center Drive, 3918 Taubman Center, SPC 5358, Ann Arbor, Michigan 48109, USA; Department of Pathology, University of Michigan, 1301 Catherine, 5240 Medical Science 1, Ann Arbor, Michigan 48109, USA
Issue Date:
2009
Publisher:
BioMed Central
Citation:
Arthritis Research & Therapy 2009, 11:R158 (doi:10.1186/ar2838)
Journal:
Arthritis Research & Therapy
Rights:
© 2009 Sarkar et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
Abstract:
INTRODUCTION:Interleukin (IL)-17 plays an important role in the pathogenesis of rheumatoid arthritis and the mouse model collagen-induced arthritis (CIA). Interferon(IFN)-gamma and IL-4 have been shown to suppress Th17 development in vitro, but their potential immunoregulatory roles in vivo are uncertain. The goals of this study were to determine the relationship between Th17 responses and disease severity in CIA and to assess regulation of IL-17 by endogenous IFN-gamma and IL-4.METHODS:DBA1/LacJ mice were immunized with type II collagen in complete Freund's adjuvant (CFA) to induce arthritis, and treated with neutralizing antibody to IFN-gamma and/or IL-4. Systemic IL-17, IFN-gamma, and IL-4 were measured in serum. At the peak of disease, cytokine production was measured by ELISA of supernatants from spleen, lymph node and paw cultures. Paws were also scored for histologic severity of arthritis.RESULTS:Joint inflammation was associated with a higher ratio of systemic IL-17/IFN-gamma. Neutralization of IFN-gamma accelerated the course of CIA and was associated with increased IL-17 levels in the serum and joints. The IFN-gamma/IL-4/IL-17 responses in the lymphoid organ were distinct from such responses in the joints. Neutralization of IL-4 led to increased arthritis only in the absence of IFN-gamma and was associated with increased bone and cartilage damage without an increase in the levels of IL-17.CONCLUSIONS:IL-4 and IFN-gamma both play protective roles in CIA, but through different mechanisms. Our data suggests that the absolute level of IL-17 is not the only determinant of joint inflammation. Instead, the balance of Th1, Th2 and Th17 cytokines control the immune events leading to joint inflammation.
EISSN:
1478-6362
DOI:
10.1186/ar2838
Version:
Final published version
Additional Links:
http://arthritis-research.com/content/11/5/R158

Full metadata record

DC FieldValue Language
dc.contributor.authorSarkar, Sujataen
dc.contributor.authorCooney, Lauraen
dc.contributor.authorWhite, Peteren
dc.contributor.authorDunlop, Deborahen
dc.contributor.authorEndres, Judithen
dc.contributor.authorJorns, Julieen
dc.contributor.authorWasco, Matthewen
dc.contributor.authorFox, Daviden
dc.date.accessioned2016-05-20T09:05:32Z-
dc.date.available2016-05-20T09:05:32Z-
dc.date.issued2009en
dc.identifier.citationArthritis Research & Therapy 2009, 11:R158 (doi:10.1186/ar2838)en
dc.identifier.doi10.1186/ar2838en
dc.identifier.urihttp://hdl.handle.net/10150/610381-
dc.description.abstractINTRODUCTION:Interleukin (IL)-17 plays an important role in the pathogenesis of rheumatoid arthritis and the mouse model collagen-induced arthritis (CIA). Interferon(IFN)-gamma and IL-4 have been shown to suppress Th17 development in vitro, but their potential immunoregulatory roles in vivo are uncertain. The goals of this study were to determine the relationship between Th17 responses and disease severity in CIA and to assess regulation of IL-17 by endogenous IFN-gamma and IL-4.METHODS:DBA1/LacJ mice were immunized with type II collagen in complete Freund's adjuvant (CFA) to induce arthritis, and treated with neutralizing antibody to IFN-gamma and/or IL-4. Systemic IL-17, IFN-gamma, and IL-4 were measured in serum. At the peak of disease, cytokine production was measured by ELISA of supernatants from spleen, lymph node and paw cultures. Paws were also scored for histologic severity of arthritis.RESULTS:Joint inflammation was associated with a higher ratio of systemic IL-17/IFN-gamma. Neutralization of IFN-gamma accelerated the course of CIA and was associated with increased IL-17 levels in the serum and joints. The IFN-gamma/IL-4/IL-17 responses in the lymphoid organ were distinct from such responses in the joints. Neutralization of IL-4 led to increased arthritis only in the absence of IFN-gamma and was associated with increased bone and cartilage damage without an increase in the levels of IL-17.CONCLUSIONS:IL-4 and IFN-gamma both play protective roles in CIA, but through different mechanisms. Our data suggests that the absolute level of IL-17 is not the only determinant of joint inflammation. Instead, the balance of Th1, Th2 and Th17 cytokines control the immune events leading to joint inflammation.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://arthritis-research.com/content/11/5/R158en
dc.rights© 2009 Sarkar et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)en
dc.titleRegulation of pathogenic IL-17 responses in collagen-induced arthritis: roles of endogenous interferon-gamma and IL-4en
dc.typeArticleen
dc.identifier.eissn1478-6362en
dc.contributor.departmentSection of Rheumatology, Department of Medicine, University of Arizona, 1501 N. Campbell Avenue, Rm 6310, Tucson, Arizona 85724, USAen
dc.contributor.departmentDivision of Rheumatology, Department of Internal Medicine, and Rheumatic Disease Core Center, University of Michigan, 1500 E Medical Center Drive, 3918 Taubman Center, SPC 5358, Ann Arbor, Michigan 48109, USAen
dc.contributor.departmentDepartment of Pathology, University of Michigan, 1301 Catherine, 5240 Medical Science 1, Ann Arbor, Michigan 48109, USAen
dc.identifier.journalArthritis Research & Therapyen
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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