Expression of interleukin-18 in human atherosclerotic plaques and relation to plaque instability.
BACKGROUND
Interleukin (IL)-18 is a potent proinflammatory cytokine with potential atherogenic properties. Its expression and role in atherosclerosis, however, are unknown.


RESULTS
In the present study, we examined stable and unstable human carotid atherosclerotic plaques retrieved by endarterectomy for the presence of IL-18 using reverse transcription-polymerase chain reaction (PCR), Western blot, and immunohistochemical techniques. IL-18 was highly expressed in the atherosclerotic plaques compared with control normal arteries and was localized mainly in plaque macrophages. IL-18 receptor was also upregulated in plaque macrophages and endothelial cells, suggesting potential biological effects. To examine the role of IL-18 in atherosclerosis, we determined the relation between IL-18 mRNA expression and signs of plaque instability using real-time quantitative PCR. Interestingly, significantly higher levels of IL-18 mRNA were found in symptomatic (unstable) plaques than asymptomatic (stable) plaques (P<0.01).


CONCLUSIONS
These results suggest, for the first time, a major role for IL-18 in atherosclerotic plaque destabilization leading to acute ischemic syndromes.
Mallat
Z
Z
Institut National de la Santé et de la Recherche Médicale, INSERM U541, Institut Fédératif de Recherche Circulation Paris VII, Hôpital Lariboisière, Paris, France. ziad.mallat@inserm.lrb.ap-hop-paris.fr
Corbaz
A
A
Scoazec
A
A
Besnard
S
S
Lesèche
G
G
Chvatchko
Y
Y
Tedgui
A
A
D000368:Aged; D001161:Arteriosclerosis / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D016893:Carotid Stenosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D053727:Interleukin-18 Receptor alpha Subunit; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology; D012333:RNA, Messenger / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000378:metabolism; D053724:Receptors, Interleukin-18; D020521:Stroke / Q000209:etiology*; D014158:Transcription, Genetic
C508572:IL18R1 protein, human; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18