title: A functional interleukin-1 receptor antagonist polymorphism influences atherosclerosis development. The interleukin-1beta:interleukin-1 receptor antagonist balance in atherosclerosis.
abstract: BACKGROUND
  Interleukin (IL)-beta plays a central role in inflammation and atherosclerosis, but levels of IL-1beta, its natural antagonist, IL-1Ra, and their balance in human atherosclerotic lesions, are unknown. Knowledge of protein levels in atherosclerosis and the influence of a functional IL-1Ra polymorphism would increase the understanding of atherosclerosis pathogenesis.
  
  
  RESULTS
  Fresh and endotoxin-stimulated explanted human atherosclerotic and normal arteries were analyzed for IL-1beta, IL-1Ra and IL-1 receptor 1 (IL-1R1) using TaqMan PCR and enzyme-linked immunosorbent assay. Two hundred forty-three survivors of a first myocardial infarction were genotyped for a polymorphism in IL-1Ra and their coronary atherosclerosis analyzed by using coronary angiography. Levels of IL-1beta, IL-1Ra and IL-1R1 mRNA were significantly increased in atherosclerotic arteries compared with normal arteries. Endotoxin stimulation increased IL-1beta levels more than IL-1Ra levels (ie, promoted a pro-inflammatory state). A polymorphism in IL-1Ra known to increase levels of IL-1Ra was associated with decreased mean coronary artery plaque area.
  
  
  CONCLUSIONS
  Activation of innate immunity changed the balance between IL-1beta and IL-1Ra in atherosclerotic arteries towards a more pro-inflammatory state. In line with this, the presence of an IL-1Ra intron 2 polymorphism known to increase IL-1Ra levels, and possibly the IL-1Ra:IL-1beta ratio, was associated with reduced coronary atherosclerosis.
authors: Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden. Peder.Olofsson@ki.se
authors: Peder S
authors: PS
authors: Olofsson
authors: Yuri
authors: Y
authors: Sheikine
authors: Ken
authors: K
authors: Jatta
authors: Mehran
authors: M
authors: Ghaderi
authors: Ann
authors: A
authors: Samnegård
authors: Per
authors: P
authors: Eriksson
authors: Allan
authors: A
authors: Sirsjö
mesh_terms: D001158:Arteries / Q000737:chemistry; D050197:Atherosclerosis / Q000209:etiology* / Q000235:genetics; D004731:Endotoxins / Q000494:pharmacology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000209:etiology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000032:analysis / Q000235:genetics*; D053583:Interleukin-1beta / Q000032:analysis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics; D011110:Polymorphism, Genetic / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D017472:Receptors, Interleukin-1 / Q000032:analysis
chemical_list: D004731:Endotoxins; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1