title: Deficiency of interleukin-1 receptor antagonist promotes neointimal formation after injury.
abstract: BACKGROUND
  The cytokine interleukin (IL)-1 is an important mediator of inflammation and cardiovascular disease. Activity of this cytokine is modulated endogenously via the IL-1 receptor antagonist (IL-1Ra). The role of IL-1Ra in neointima formation after injury, however, is poorly understood.
  
  
  RESULTS
  Using IL-1Ra-deficient (IL-1Ra-/-; backcrossed 8 generations into the C57BL/6J background) and wild-type (IL-1Ra+/+) mice, we investigated neointimal formation 3 weeks after femoral artery injury induced by an external vascular cuff model. Intima and media thicknesses were measured, and the intima/media ratio was calculated. The mean intimal thickness and the intima/media ratio of IL-1Ra-/- mice increased by 249% (31.8+/-2.9 microm [n=10] versus 9.1+/-0.7 microm [n=10]; P<0.0001) and 257% (2.5+/-0.2 versus 0.7+/-0.1; P<0.0001), respectively, compared with IL-1Ra+/+ mice. No significant differences were observed in the medial thickness. Control immunostaining for IL-1Ra in injured vessels localized IL-1beta and the endogenous inhibitor in the endothelium and inflammatory cells of the adventitia in IL-1Ra+/+ but not IL-1Ra-/- mice.
  
  
  CONCLUSIONS
  The absence of IL-1Ra promotes neointimal formation in mice after injury. These results suggest that endogenous IL-1Ra may suppress other occlusive vascular responses to injury, such as atherosclerosis and restenosis after angioplasty.
authors.affiliation: First Department of Internal Medicine, National Defense Medical College, 3-2, Namiki, Tokorozawa, Saitama, 359-8513, Japan. isoda@me.ndmc.ac.jp
authors.forename: Kikuo
authors.initials: K
authors.lastname: Isoda
authors.forename: Masaru
authors.initials: M
authors.lastname: Shiigai
authors.forename: Norio
authors.initials: N
authors.lastname: Ishigami
authors.forename: Taizo
authors.initials: T
authors.lastname: Matsuki
authors.forename: Reiko
authors.initials: R
authors.lastname: Horai
authors.forename: Kenichirou
authors.initials: K
authors.lastname: Nishikawa
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kusuhara
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nishida
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Ohsuzu
mesh_terms: D000818:Animals; D002455:Cell Division / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D005263:Femoral Artery / Q000293:injuries* / Q000378:metabolism / Q000473:pathology*; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006965:Hyperplasia / Q000473:pathology; D007150:Immunohistochemistry; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010641:Phenotype; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D017539:Tunica Intima / Q000293:injuries* / Q000378:metabolism / Q000473:pathology*
chemical_list: C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D018809:Proliferating Cell Nuclear Antigen; D012795:Sialoglycoproteins