Interleukin (IL)-1 is a proinflammatory cytokine that plays important roles in inflammation, host defense, and the neuro-immuno-endocrine network. IL-1 receptor antagonist (ra) is an endogenous inhibitor of IL-1 and is supposed to regulate IL-1 activity. However, its pathophysiological roles in a body remain largely unknown. To elucidate the roles of IL-1ra, IL-1ra–deficient mice were produced by gene targeting, and pathology was analyzed on different genetic backgrounds. We found that all of the mice on a BALB/cA background, but not those on a C57BL/6J background, spontaneously developed chronic inflammatory polyarthropathy. Histopathology showed marked synovial and periarticular inflammation, with articular erosion caused by invasion of granulation tissues closely resembling that of rheumatoid arthritis in humans. Moreover, elevated levels of antibodies against immunoglobulins, type II collagen, and double-stranded DNA were detected in these mice, suggesting development of autoimmunity. Proinflammatory cytokines such as IL-1β, IL-6, and tumor necrosis factor α were overexpressed in the joints, indicating regulatory roles of IL-1ra in the cytokine network. We thus show that IL-1ra gene deficiency causes autoimmunity and joint-specific inflammation and suggest that IL-1ra is important in maintaining homeostasis of the immune system. Possible involvement of IL-1ra gene deficiency in RA will be discussed.
Skip Nav Destination
Article navigation
17 January 2000
Article|
January 17 2000
Development of Chronic Inflammatory Arthropathy Resembling Rheumatoid Arthritis in Interleukin 1 Receptor Antagonist–Deficient Mice
Reiko Horai,
Reiko Horai
aCenter for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
Search for other works by this author on:
Shinobu Saijo,
Shinobu Saijo
aCenter for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
Search for other works by this author on:
Hidetoshi Tanioka,
Hidetoshi Tanioka
bDevelopmental Research Laboratories, Santen Pharmaceutical Company Limited, Osaka 533-8651, Japan
Search for other works by this author on:
Susumu Nakae,
Susumu Nakae
aCenter for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
Search for other works by this author on:
Katsuko Sudo,
Katsuko Sudo
aCenter for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
Search for other works by this author on:
Akihiko Okahara,
Akihiko Okahara
bDevelopmental Research Laboratories, Santen Pharmaceutical Company Limited, Osaka 533-8651, Japan
Search for other works by this author on:
Toshimi Ikuse,
Toshimi Ikuse
bDevelopmental Research Laboratories, Santen Pharmaceutical Company Limited, Osaka 533-8651, Japan
Search for other works by this author on:
Masahide Asano,
Masahide Asano
aCenter for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
Search for other works by this author on:
Yoichiro Iwakura
Yoichiro Iwakura
aCenter for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
Search for other works by this author on:
Reiko Horai
aCenter for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
Shinobu Saijo
aCenter for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
Hidetoshi Tanioka
bDevelopmental Research Laboratories, Santen Pharmaceutical Company Limited, Osaka 533-8651, Japan
Susumu Nakae
aCenter for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
Katsuko Sudo
aCenter for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
Akihiko Okahara
bDevelopmental Research Laboratories, Santen Pharmaceutical Company Limited, Osaka 533-8651, Japan
Toshimi Ikuse
bDevelopmental Research Laboratories, Santen Pharmaceutical Company Limited, Osaka 533-8651, Japan
Masahide Asano
aCenter for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
Yoichiro Iwakura
aCenter for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
Abbreviations used in this paper: COX, cyclooxygenase; IIC, type II collagen; ra, receptor antagonist; RA, rheumatoid arthritis; RF, rheumatoid factor.
Received:
July 20 1999
Revision Requested:
October 06 1999
Accepted:
October 20 1999
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2000 The Rockefeller University Press
2000
The Rockefeller University Press
J Exp Med (2000) 191 (2): 313–320.
Article history
Received:
July 20 1999
Revision Requested:
October 06 1999
Accepted:
October 20 1999
Citation
Reiko Horai, Shinobu Saijo, Hidetoshi Tanioka, Susumu Nakae, Katsuko Sudo, Akihiko Okahara, Toshimi Ikuse, Masahide Asano, Yoichiro Iwakura; Development of Chronic Inflammatory Arthropathy Resembling Rheumatoid Arthritis in Interleukin 1 Receptor Antagonist–Deficient Mice. J Exp Med 17 January 2000; 191 (2): 313–320. doi: https://doi.org/10.1084/jem.191.2.313
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
Email alerts
Advertisement