Related Experiment Video
Updated: Aug 21, 2026
Quantitative Analysis of Cellular Composition in Advanced Atherosclerotic Lesions of Smooth Muscle Cell Lineage-Tracing Mice
Published on: February 20, 2019
IL-6 and the acute phase response in murine atherosclerosis
1Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Insights
Interleukin-6 (IL-6) and the acute phase response (APR) are not significant factors in the development of atherosclerosis. This study found minimal differences in lesion development in mice lacking IL-6, suggesting other factors are more critical in heart disease.
Area of Science:
- Cardiovascular Research
- Immunology
- Genetics
Background:
- C-reactive protein (CRP) and the acute phase response (APR) are linked to atherosclerotic heart disease.
- Interleukin-6 (IL-6) regulates CRP and APR, and is also a potential heart disease risk factor.
Purpose of the Study:
- To investigate the direct role of IL-6 in the development of atherosclerosis.
- To determine if IL-6 and the APR significantly contribute to atherogenesis.
Main Methods:
- Generated IL-6 knockout mice crossed with LDL receptor (LDL-R) knockout mice.
- Evaluated atherosclerotic lesion development on Chow, Western, and Paigen diets.
- Assessed APR gene expression in response to dietary challenges.
Main Results:
- Paigen diet induced APR genes in LDL-R knockout mice, but not in IL-6/LDL-R knockout mice.
- No significant differences in atherosclerotic lesion development were observed between LDL-R knockout and IL-6/LDL-R knockout mice.
- Modest, non-statistically significant variations in lesion development were noted.
Conclusions:
- IL-6 and the acute phase response may play a less critical role in atherogenesis than previously suggested.
- Findings challenge the established significance of IL-6 in the development of atherosclerotic heart disease.
Abstract:
Numerous studies have implicated C-reactive protein (CRP) and the acute phase response (APR) in the development of atherosclerotic heart disease. Interleukin (IL)-6, which regulates both CRP expression and the APR, has also been identified as a risk factor for heart disease. To more directly evaluate the role of IL-6 in the development of atherosclerosis, IL-6 knockout mice were crossed with atherosclerosis prone LDL receptor (LDL-R) knockout mice. Lesion development was evaluated on Chow, Western type and Paigen diets. As anticipated, the Paigen diet stimulated the expression of APR genes in LDL-R[-/-] mice, but not IL-6[-/-]/LDL-R[-/-] mice. Despite this difference in acute phase response, only modest and statistically not significant differences were noted in the development of atherosclerotic lesions in LDL-R[-/-] and IL-6[-/-]/LDL-R[-/-] mice. These observations suggest that IL-6 and the acute phase response may not play as significant role in atherogenesis as other studies have indicated.
