title: Proatherogenic effect of interleukin-18 is exerted with high-fat diet, but not with normal diet in spontaneously hyperlipidemic mice.
abstract: OBJECTIVE
  It has been considered that interleukin (IL)-18, a T helper 1(Th1) type cytokine, has a promoting effect on atherosclerosis development. A previous mouse study demonstrated that short-term exogenous IL-18 promoted atherosclerosis through a Th1 type immune response; however, the serum IL-18 may have increased greatly beyond its physiological range, and the effect of increased serum IL-18 on atherosclerosis development has not been investigated under different conditions of dietary fat content. The purpose of this study was to reveal the effect of increased serum IL-18 within its physiological fluctuations on atherosclerosis development under different conditions of dietary fat content.
  
  
  METHODS
  Spontaneously hyperlipidemic (SHL) mice were systemically supplied with IL-18 for 10 weeks by means of an in vivo gene transfer system with a high-fat diet containing 0.15% cholesterol or a normal diet.
  
  
  RESULTS
  Serum IL-18 steadily elevated within its physiological fluctuations. An atherosclerotic lesion area in the aortic root significantly increased with a high-fat diet. Systemic cytokine balance shifted to a Th1-dominant state, and IL-12 mRNA in the arterial wall significantly increased with a high-fat diet; however, these findings were not observed with a normal diet.
  
  
  CONCLUSIONS
  It was suggested that the proatherogenic effect of IL-18 is physiologically exerted exclusively with a high-fat diet through Th1 type immune responses, but not with a normal diet.
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Imai
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Oikawa
authors.forename: Akira
authors.initials: A
authors.lastname: Shimada
authors.forename: Sumito
authors.initials: S
authors.lastname: Oguchi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Takamiya
authors.forename: Takeshi
authors.initials: T
authors.lastname: Katsuki
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Okubo
authors.forename: Tadashi
authors.initials: T
authors.lastname: Osaki
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tahara
authors.forename: Yoshibumi
authors.initials: Y
authors.lastname: Matsushima
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Miyazaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004041:Dietary Fats / Q000008:administration & dosage*; D004797:Enzyme-Linked Immunosorbent Assay; D006949:Hyperlipidemias / Q000235:genetics / Q000503:physiopathology*; D020382:Interleukin-18 / Q000502:physiology*; D008297:Male; D051379:Mice; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D016207:Cytokines; D004041:Dietary Fats; D020382:Interleukin-18; D012333:RNA, Messenger