Proatherogenic effect of interleukin-18 is exerted with high-fat diet, but not with normal diet in spontaneously hyperlipidemic mice

Takatoshi Imai, Yoichi Oikawa, Akira Shimada, Sumito Oguchi, Yoshihiro Takamiya, Takeshi Katsuki, Yoshiaki Okubo, Tadashi Osaki, Hideaki Tahara, Yoshibumi Matsushima, Jun Ichi Miyazaki, Hiroshi Itoh

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3 Citations (Scopus)

Abstract

Aim: 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.

Original languageEnglish
Pages (from-to)1090-1101
Number of pages12
JournalJournal of atherosclerosis and thrombosis
Volume18
Issue number12
DOIs
Publication statusPublished - 2011 Dec 22

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Keywords

  • Atherosclerosis
  • Interleukin (IL)-18
  • Spontaneously hyperlipidemic (SHL) mouse
  • T helper 1(Th1)

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine
  • Biochemistry, medical

Cite this

Imai, T., Oikawa, Y., Shimada, A., Oguchi, S., Takamiya, Y., Katsuki, T., Okubo, Y., Osaki, T., Tahara, H., Matsushima, Y., Miyazaki, J. I., & Itoh, H. (2011). Proatherogenic effect of interleukin-18 is exerted with high-fat diet, but not with normal diet in spontaneously hyperlipidemic mice. Journal of atherosclerosis and thrombosis, 18(12), 1090-1101. https://doi.org/10.5551/jat.7567