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Reduced atherosclerosis in interleukin-18 deficient apolipoprotein E-knockout mice
Rima Elhage1, Jacek Jawien, Mats Rudling
1Department of Medicine at Karolinska Hospital and Center for Molecular Medicine L8:03, Karolinska Institute, SE-17176 Stockholm, Sweden.
Cardiovascular Research
|June 28, 2003
Summary
Interleukin-18 (IL-18) deficiency in mice significantly reduced atherosclerosis development and T helper 1 (Th1) immune activity. This suggests IL-18 plays a proatherogenic role in this inflammatory disease.
Area of Science:
- Immunology
- Cardiovascular Research
- Inflammation
Background:
- Atherosclerosis is an inflammatory condition where T helper 1 (Th1) immunity is implicated.
- Th1 effector cells, producing interferon-gamma (IFN-gamma), develop from naive CD4+ T cells stimulated by IL-18 and IL-12.
Purpose of the Study:
- To investigate the proatherogenic role of the Th1 pathway.
- To determine the direct impact of Interleukin-18 (IL-18) deficiency on atherosclerosis progression.
Main Methods:
- Apolipoprotein E-deficient (apoE(-/-)) mice were crossed with IL-18 knockout mice (IL-18(-/-)).
- Atherosclerosis was quantified in the aortic root of the resulting offspring.
- Analysis included lesion size, cellular composition, and immune cell activity.
Main Results:
- IL-18 deficient apoE(-/-) mice showed significantly reduced atherosclerotic lesion size compared to controls.
- Lesion cells exhibited decreased IFN-gamma stimulation and an increased proportion of stable smooth muscle cells.
- Despite reduced atherosclerosis, IL-18 deficient mice had higher serum cholesterol and triglyceride levels.
Conclusions:
- Reduced atherosclerosis and Th1 activity were observed in IL-18 deficient apoE(-/-) mice.
- These findings support a proatherogenic role for IL-18 in the development of atherosclerosis.
- The study highlights a complex interplay between IL-18, Th1 immunity, and lipid metabolism in atherosclerosis.