RGD Reference Report - Impact of IL-1 signalling on experimental uveitis and arthritis. - Rat Genome Database

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

Authors: Planck, SR  Woods, A  Clowers, JS  Nicklin, MJ  Rosenbaum, JT  Rosenzweig, HL 
Citation: Planck SR, etal., Ann Rheum Dis. 2012 May;71(5):753-60. doi: 10.1136/annrheumdis-2011-200556. Epub 2012 Jan 20.
RGD ID: 8549801
Pubmed: PMID:22267332   (View Abstract at PubMed)
PMCID: PMC3335437   (View Article at PubMed Central)
DOI: DOI:10.1136/annrheumdis-2011-200556   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Endotoxin-Induced Uveitis susceptibilityISOIl1rn (Mus musculus)8549801; 8549801 RGD 
Endotoxin-Induced Uveitis susceptibilityIMP 8549801 RGD 
Experimental Arthritis  ISOIl1rn (Mus musculus)8549801; 8549801 RGD 
Experimental Arthritis  IMP 8549801 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il1rn  (interleukin 1 receptor antagonist)

Genes (Mus musculus)
Il1rn  (interleukin 1 receptor antagonist)

Genes (Homo sapiens)
IL1RN  (interleukin 1 receptor antagonist)

Additional Information