Abstract:
:The pro-inflammatory cytokines tumor necrosis factor (TNF) and interleukin-1 (IL-1) have been shown to be primary mediators in the pathogenesis of chronic inflammatory joint diseases. However, the relative contributions of these molecules to the development and progression of disease is not known. In the present study, we have investigated the involvement of the type I IL-1 receptor in the development and progression of chronic arthritis in a previously described TNF-transgenic mouse model of this disease. A neutralizing monoclonal antibody to the murine type I IL-1 receptor was injected intraperitoneally three times a week from birth to 9 weeks of age. In the positive control group of untreated transgenic mice the incidence of arthritis was 100% after 9 weeks of age. The injection of normal hamster IgG did not influence the incidence or development of arthritis. In contrast, the injection of antibody to the type I IL-1 receptor completely prevented the development of arthritis. Clinical evaluation of disease was confirmed histologically, anti-receptor antibody-treated mice showed no sign of arthritic change. Moreover, the analysis of sera taken at the end of the study period showed that the neutralization of arthritis by IL-1 receptor antibody treatment was accompanied by significantly lower levels of circulating human TNF compared to the control groups and to untreated transgenic mice prior to disease onset. Taken together, these results show that IL-1 signaling blockade exerts a direct negative feedback effect on TNF production. Our results show that in TNF-transgenic mice the IL-1 receptor accepts the whole pathogenic load of TNF, thereby acting as a potent downstream mediator in the pathogenesis of chronic arthritis.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Probert L,Plows D,Kontogeorgos G,Kollias Gdoi
10.1002/eji.1830250647subject
Has Abstractpub_date
1995-06-01 00:00:00pages
1794-7issue
6eissn
0014-2980issn
1521-4141journal_volume
25pub_type
杂志文章abstract::The study of the immunology of schistosomiasis has allowed a clear understanding of the basic mechanisms of resistance, emphasizing the important role played by cellular and humoral factors. Whereas the production of polyclonal or monoclonal antibodies and the precise inventory of immune effector mechanisms in the rat...
journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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doi:10.1002/eji.1830250611
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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doi:10.1002/eji.1830170906
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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