title: Inhibition of interleukin-1 but not tumor necrosis factor suppresses neovascularization in rat models of corneal angiogenesis and adjuvant arthritis.
abstract: OBJECTIVE
  To assess the capacities of the cytokine inhibitors interleukin-1 receptor antagonist (IL-1Ra; anakinra) and PEGylated soluble tumor necrosis factor receptor I (PEG sTNFRI; pegsunercept) to suppress neovascularization.
  
  
  METHODS
  A corneal angiogenesis assay was performed by implanting nylon discs impregnated with an angiogenic stimulator (basic fibroblast growth factor or vascular endothelial growth factor) into one cornea of female Sprague-Dawley rats. Animals were treated with IL-1Ra or PEG sTNFRI for 7 days, after which new vessels were quantified. In a parallel study, male Lewis rats with mycobacteria-induced adjuvant-induced arthritis were treated with IL-1Ra or PEG sTNFRI for 7 days beginning at disease onset, after which scores for inflammation and bone erosion as well as capillary counts were acquired from sections of arthritic hind paws.
  
  
  RESULTS
  Treatment with IL-1Ra yielded a dose-dependent reduction in growth factor-induced corneal angiogenesis, while PEG sTNFRI did not. IL-1Ra, but not PEG sTNFRI, significantly reduced the number of capillaries in arthritic paws, even though both anticytokines reduced inflammation and bone erosion to a similar degree.
  
  
  CONCLUSIONS
  These data support a major role for IL-1, but not TNFalpha, in angiogenesis and suggest that an additional antiarthritic mechanism afforded by IL-1 inhibitors, but not anti-TNF agents, is the suppression of the angiogenic component of pannus.
authors.affiliation: Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Coxon
authors.forename: Brad
authors.initials: B
authors.lastname: Bolon
authors.forename: Juan
authors.initials: J
authors.lastname: Estrada
authors.forename: Stephen
authors.initials: S
authors.lastname: Kaufman
authors.forename: Sheila
authors.initials: S
authors.lastname: Scully
authors.forename: Alana
authors.initials: A
authors.lastname: Rattan
authors.forename: Diane
authors.initials: D
authors.lastname: Duryea
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Hu
authors.forename: Karen
authors.initials: K
authors.lastname: Rex
authors.forename: Efrain
authors.initials: E
authors.lastname: Pacheco
authors.forename: Gwyneth
authors.initials: G
authors.lastname: Van
authors.forename: Debra
authors.initials: D
authors.lastname: Zack
authors.forename: Ulrich
authors.initials: U
authors.lastname: Feige
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D016510:Corneal Neovascularization / Q000188:drug therapy* / Q000276:immunology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000276:immunology; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D008297:Male; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics; D011092:Polyethylene Glycols / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D017472:Receptors, Interleukin-1 / Q000235:genetics; D053573:Receptors, Interleukin-1 Type I; D053574:Receptors, Interleukin-1 Type II; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000494:pharmacology*; D012795:Sialoglycoproteins / Q000494:pharmacology; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D053574:Receptors, Interleukin-1 Type II; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D012795:Sialoglycoproteins; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; C069521:recombinant human tumor necrosis factor-binding protein-1; D011092:Polyethylene Glycols; C577771:PEGylated soluble tumor necrosis factor receptor I