title: 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.
  
  
  CONCLUSIONS
  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.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Planck
authors.forename: April
authors.initials: A
authors.lastname: Woods
authors.forename: Jenna S
authors.initials: JS
authors.lastname: Clowers
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Nicklin
authors.forename: James T
authors.initials: JT
authors.lastname: Rosenbaum
authors.forename: Holly L
authors.initials: HL
authors.lastname: Rosenzweig
mesh_terms: D000818:Animals; D001168:Arthritis / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005123:Eye / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005260:Female; D053590:Interleukin 1 Receptor Antagonist Protein / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism*; D007596:Joints / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018715:Microscopy, Video / Q000379:methods; D009928:Organ Specificity; D015398:Signal Transduction; D014605:Uveitis / Q000150:complications / Q000378:metabolism / Q000473:pathology*
chemical_list: C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008070:Lipopolysaccharides