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TNF-alpha: a link between hypertriglyceridaemia and inflammation in SLE patients with cardiovascular disease
E Svenungsson1, G Z Fei, K Jensen-Urstad
1Department of Medicine, Rheumatology Unit, Karolinska Institutet, Stockholm, Sweden. elisabet.svenungsson@medks.ki.se
Insights
Tumour necrosis factor-alpha (TNF-alpha) and its soluble receptors are elevated in patients with systemic lupus erythematosus (SLE) and cardiovascular disease (CVD). Elevated TNF-alpha is linked to hypertriglyceridemia and atherosclerosis in SLE-related CVD.
Area of Science:
- Immunology
- Cardiology
- Rheumatology
Background:
- Systemic lupus erythematosus (SLE) patients face a high risk of cardiovascular disease (CVD).
- Tumour necrosis factor-alpha (TNF-alpha) is implicated in the pathophysiology of both SLE and CVD.
- The role of TNF-alpha and its soluble receptors in SLE-related CVD requires further investigation.
Purpose of the Study:
- To investigate the association between TNF-alpha, soluble TNF-alpha receptors (sTNFR1, sTNFR2), and CVD in SLE patients.
- To explore the relationship between TNF-alpha and cardiovascular risk factors in SLE.
Main Methods:
- Cross-sectional study comparing SLE patients with CVD (cases), SLE patients without CVD (controls), and population-based controls.
- Plasma concentrations of TNF-alpha, sTNFR1, and sTNFR2 were measured using ELISA.
- Correlation analyses were performed to assess relationships between TNF-alpha and cardiovascular risk factors.
Main Results:
- TNF-alpha, sTNFR1, and sTNFR2 levels were significantly higher in SLE cases compared to SLE controls and population controls.
- SLE controls also exhibited higher levels of these markers than population controls.
- In SLE cases, TNF-alpha strongly correlated with triglycerides, VLDL triglycerides, VLDL cholesterol, and waist-hip ratio.
Conclusions:
- TNF-alpha may play a significant role in SLE-related CVD by contributing to hypertriglyceridemia and promoting atherosclerosis.
- sTNFR1 and sTNFR2 are strongly associated with CVD in SLE, but their precise roles need further elucidation.
Abstract:
Patients with systemic lupus erythematosus (SLE) are at high risk of cardiovascular disease (CVD). Tumour necrosis factor-alpha (TNF-alpha) has been implicated in the pathophysiological processes of both SLE and CVD. This study focuses on the role of TNF-alpha and its soluble receptors in SLE-related CVD. In summary, 26 women (52 +/- 8.2 years) with SLE and a history of CVD (SLE cases) we compared with 26 age-matched women with SLE and no clinical manifestations of CVD (SLE controls) and 26 age-matched population-based control women (population controls). Plasma concentrations of circulating TNF-alpha, TNF-alpha receptor 1 (sTNFR1) and TNF-a receptor 2 (sTNFR2) were determined by ELISA. TNF-alpha, sTNFR1 and sTNFR2 were raised in SLE cases as compared to SLE controls (P = 0.009; P = 0.001; P = 0.001, respectively), and SLE controls had higher levels than population controls (P = 0.001; P = 0.02; P = 0.001, respectively). Exclusively in the SLE case group there was a striking positive correlation between TNF-alpha and plasma triglycerides (r = 0.57, P < 0.002), VLDL triglycerides (r = 0.54, P = 0.004) and VLDL cholesterol (r = 0.58, P = 0.002). Furthermore, TNF-alpha correlated with the waist-hip ratio but not with estimated insulin resistance. TNF-alpha may thus be a major factor in SLE-related CVD acting both by contributing to hypertriglyceridaemia and by promoting atherosclerosis-related inflammation. sTNFR1 and sTNFR2 are strongly associated with CVD in SLE but their exact roles in disease development remain to be elucidated.
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