Impact of IL-1 signalling on experimental uveitis and arthritis.

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.

• Authors: Stephen R Planck, April Woods, Jenna S Clowers, Martin J Nicklin, James T Rosenbaum, Holly L Rosenzweig
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 71 Issue 5 Pg. 753-60 (May 2012) ISSN: 1468-2060 [Electronic] England
• PMID: 22267332 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Il1rn protein, mouse
• Interleukin 1 Receptor Antagonist Protein
• Interleukin-1
• Lipopolysaccharides

Topics

• Animals
• Arthritis (complications, metabolism, pathology)
• Disease Models, Animal
• Eye (drug effects, metabolism, pathology)
• Female
• Interleukin 1 Receptor Antagonist Protein (deficiency, genetics, metabolism)
• Interleukin-1 (metabolism)
• Joints (metabolism, pathology)
• Lipopolysaccharides (pharmacology)
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Microscopy, Video (methods)
• Organ Specificity
• Signal Transduction
• Uveitis (complications, metabolism, pathology)