Impact of IL-1 Signalling on Experimental Uveitis and Arthritis

Overview

Journal Ann Rheum Dis

Specialty Rheumatology

Date 2012 Jan 24

PMID 22267332

Citations 15

Authors

Stephen R Planck

April Woods

Jenna S Clowers

Martin J Nicklin

James T Rosenbaum

Holly L Rosenzweig

Affiliations

Soon will be listed here.

Abstract

Background: Uveitis, or inflammatory eye disease, is a common extra-articular manifestation of many systemic autoinflammatory diseases involving the joints. Anakinra (recombinant interleukin (IL)-1 receptor antagonist (Ra)) is an effective therapy in several arthritic diseases; yet, few studies have investigated the extent to which IL-1 signalling or IL-1Ra influences the onset and/or severity of uveitis.

Objective: To seek possible links between arthritis and uveitis pathogenesis related to IL-1 signalling.

Methods: The eyes of IL-1Ra-deficient BALB/c mice were monitored histologically and by intravital videomicroscopy to determine if uveitis developed along with the expected spontaneous arthritis in ankles and knees. Expression levels of IL-1R and its negative regulators (IL-1Ra, IL-1RII, IL-1RAcP and single Ig IL-1R-related molecule) in eye and joint tissues were compared. Differences in uveitis induced by intraocular injection of lipopolysaccharide (LPS) in mice lacking IL-1R or IL-1Ra were assessed.

Results: Deficiency in IL-1Ra predisposes to spontaneous arthritis, which is exacerbated by previous systemic LPS exposure. The eye, however, does not develop inflammatory disease despite the progressive arthritis or LPS exposure. Organ-specific expression patterns for IL-1Ra and negative regulators of IL-1 activity were observed that appear to predict predisposition to inflammation in each location in IL-1Ra knockout mice. The eye is extremely sensitive to locally administered LPS, and IL-1Ra deficiency markedly exacerbates the resulting uveitis.

Conclusion: This study demonstrates that IL-1Ra plays an important role in suppressing local responses in eyes injected with LPS and that there is discordance between murine eyes and joints in the extent to which IL-1Ra protects against spontaneous inflammation.

Citing Articles

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Intraocular dendritic cells characterize HLA-B27-associated acute anterior uveitis.

Kasper M, Heming M, Schafflick D, Li X, Lautwein T, Meyer Zu Horste M Elife. 2021; 10.

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Increase in the Number of Bone Marrow Osteoclast Precursors at Different Skeletal Sites, Particularly in Long Bone and Jaw Marrow in Mice Lacking IL-1RA.

Ascone G, Cao Y, Jansen I, Di Ceglie I, van den Bosch M, Blom A Int J Mol Sci. 2020; 21(11).

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