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Biomedical subjects

Johan Frostegård

Publications and source records attributed to Johan Frostegård.

At least 19 recordsLinked to original sources

A Paleolithic diet confers higher insulin sensitivity, lower C-reactive protein and lower blood pressure than a cereal-based diet in domestic pigs.

BACKGROUND: A Paleolithic diet has been suggested to be more in concordance with human evolutionary legacy than a cereal based diet. This might explain the lower incidence among hunter-gatherers of diseases of affluence such as type 2 diabetes, obesity and cardiovascular disease. The aim of this study was to experimentally study the long-term effect of a Paleolithic diet on risk factors for these diseases in domestic pigs. We examined glucose tolerance, post-challenge insulin response, plasma C-reactive protein and blood pressure after 15 months on Paleolithic diet in comparison with a cereal based swine feed. METHODS: Upon weaning twenty-four piglets were randomly allocated either to cereal based swine feed (Cereal group) or cereal free Paleolithic diet consisting of vegetables, fruit, meat and a small amount of tubers (Paleolithic group). At 17 months of age an intravenous glucose tolerance test was performed and pancreas specimens were collected for immunohistochemistry. Group comparisons of continuous variables were made by use of the t-test. P < 0.05 was chosen for statistical significance. Simple and multivariate correlations were evaluated by use of linear regression analysis. RESULTS: At the end of the study the Paleolithic group weighed 22% less and had 43% lower subcutaneous fat thickness at mid sternum. No significant difference was seen in fasting glucose between groups. Dynamic insulin sensitivity was significantly higher (p = 0.004) and the insulin response was significantly lower in the Paleolithic group (p = 0.001). The geometric mean of C-reactive protein was 82% lower (p = 0.0007) and intra-arterial diastolic blood pressure was 13% lower in the Paleolithic group (p = 0.007). In evaluations of multivariate correlations, diet emerged as the strongest explanatory variable for the variations in dynamic insulin sensitivity, insulin response, C-reactive protein and diastolic blood pressure when compared to other relevant variables such as weight and subcutaneous fat thickness at mid sternum. There was no obvious immunohistochemical difference in pancreatic islets between the groups, but leukocytes were clearly more frequent in sampled pancreas from the Cereal group. CONCLUSION: This study in domestic pigs suggests that a Paleolithic diet conferred higher insulin sensitivity, lower C-reactive protein and lower blood pressure when compared to a cereal based diet.

Journal Article↗

Systemic lupus-erythematosus: deoxyribonuclease 1 in necrotic chromatin disposal.

Systemic lupus-erythematosus is an auto-immune-disease characterized by pathogenic anti-nuclear auto-antibodies. These form immune-complexes that after deposition at basal membranes at various locations initiate inflammatory reactions. There is a clear genetic and gender predisposition (females are affected 10 times more frequently), but also infectious agents and further environmental factors have been shown to be causative for the initiation of the disease. It has been suggested that the auto-antibodies arise after release and/or inefficient removal of nuclear components during cell death (defective cellular "waste disposal" theory). So far, increased apoptotic cell death has been made responsible, but recent data suggest that defective cellular waste disposal during/after necrosis may also lead to the release and prolonged exposure of nuclear components. Here, we concentrate on chromatin disposal during necrosis and the involvement of Deoxyribonuclease 1 in this process with respect to its possible role in the prevention of anti-nuclear auto-immunity.

Animals↗

Antibodies of IgM subclass to phosphorylcholine and oxidized LDL are protective factors for atherosclerosis in patients with hypertension.

OBJECTIVE: To determine the importance of antibodies against phosphorylcholine (PC) and oxidized low density lipoprotein (OxLDL) for development of atherosclerosis. METHODS AND RESULTS: Two hundred and twenty six individuals with established hypertension (diastolic pressure > 95mmHg) were from European Lacidipine Study on Atherosclerosis. Antibodies of IgG and IgM subclass were tested by ELISA against PC (aPC), cupper-oxidized (ox)- or malondialdehyde (MDA)-modified LDL. High-sensitivity C-reactive protein was measured by nephelometry. As a surrogate measure of atherosclerosis, we used the mean of the maximum intima-media thicknesses (IMT) in the far walls of common carotids and bifurcations was determined by ultrasonography at the time of enrolment, and 4 years following enrolment. aPC could be competed out by PC and OxLDL, while cardiolipin (CL) and beta2-glycoprotein I (beta2GPI) were less effective and phosphatidylserine (PS) not at all. Increases in IMT at follow-up were less common in subjects which at the time of enrolment had high IgM aPC (both 75th and 90th; odds ratios: 0.46; CI: 0.25-0.85; 0.36; CI: 0.15-0.87) and high IgM aOxLDL and aMDA-LDL (90th; odds ratios 0.27; p = 0.01; CI: 0.11-0.69 and 0.27; p = 0.01; CI: 0.11-0.69). CRP was unrelated to IMT-changes. The relationship between IgM aPC, aOxLDL and aMDA-LDL and changes in IMT was independent of age, treatment with atenolol or lacidipine, smoking and lipids. Women had higher levels of IgM antibodies tested (p < 0.05). CONCLUSIONS: High levels of IgM-antibodies against PC and OxLDL predict a favourable outcome in the development of carotid atherosclerosis in hypertensive subjects. Whether these antibodies could be used therapeutically deserves further study.

Cardiolipins↗

Annexin A5 in cardiovascular disease and systemic lupus erythematosus.

Atherosclerosis, a major cause of disease and death from cardiovascular disease (CVD), is an inflammatory disease characterized by T cell and monocyte/macrophage infiltration in the intima of large arteries. During recent years and with improved treatment of acute disease manifestations, it has become clear that the risk of CVD is very high in systemic lupus erythematosus (SLE), often considered a prototypic autoimmune disease. A combination of traditional and non-traditional risk factors, including dyslipidemia, inflammation, antiphospholipid antibodies (aPL) and lipid oxidation are related to CVD in SLE. aPL are highly thrombogenic, and possible mechanisms include direct effects of aPL on endothelial and other cells, and interference with coagulation reactions. More than a thousand proteins of the annexin-superfamily are expressed in eukaryotes. Annexins are ubiquitous, highly conserved, predominantly intracellular proteins, widely distributed in tissues. Annexin A5 (ANXA5) is an important member of the annexin family due to its antithrombotic properties. These are believed to be caused by it forming a two-dimensional protective shield, covering exposed potentially thrombogenic cell surfaces. Recently, ANXA5 has been implicated in SLE since aPL interfere with ANXA5 binding to placental trophoblasts, causing microthrombosis and miscarriage, a rather common complication in SLE. We recently demonstrated that ANXA5 may play a role in CVD and is abundant in late-stage atherosclerotic lesions. Sera from SLE-patients with a history of CVD inhibited ANXA5 binding to endothelium, caused by IgG antibodies, to a significant degree aPL. This review will focus on potential involvement of ANXA5 in pathogenesis of CVD, particularly caused by underlying atherosclerosis and atherothrombosis.

Animals↗

Atherosclerosis in patients with autoimmune disorders.

Recent findings indicate that presence of activated immune competent cells and inflammation are typical of atherosclerosis, the main cause of cardiovascular disease (CVD). The risk of CVD is very high in a prototypic autoimmune disease, systemic lupus erythematosus (SLE), and is also raised in other autoimmune diseases such as rheumatoid arthritis. Autoimmunity-related CVD and atherosclerosis are important clinical problems. They may also shed light on interactions between immune reactions and atherosclerosis development and manifestations, not least in women, who have a much higher risk of autoimmune disease than men. In general, a combination of traditional and nontraditional risk factors, including dyslipidemia (and to a varying degree, hypertension, diabetes, and smoking), inflammation, antiphospholipid antibodies (aPLs), and lipid oxidation, contribute to CVD in autoimmune diseases. Premature atherosclerosis is likely to be a major underlying mechanism, although distinctive features, if any, of autoimmunity-related atherosclerosis compared with "normal" atherosclerosis are not clear. One interesting possibility is that factors such as inflammation, neoepitopes on endothelial cells, or aPLs make atherosclerotic lesions in autoimmune disease more prone to rupture than in "normal" atherosclerosis. Some cases of autoimmunity-related CVD may be more related to thrombosis than atherosclerosis. Whether premature atherosclerosis is a general feature of autoimmune diseases such as SLE or only affects a subgroup of patients whereas others do not have an increased risk remains to be demonstrated. Treatment of patients with autoimmune disease should also include CVD aspects and be focused on traditional risk factors as well as on disease-related factors. Hopefully novel therapeutic principles will be developed that target the causes of the inflammation present in atherosclerotic lesions.

Atherosclerosis↗

Lipid peroxidation is enhanced in patients with systemic lupus erythematosus and is associated with arterial and renal disease manifestations.

OBJECTIVE: Cardiovascular disease with premature atherosclerosis is common in patients with systemic lupus erythematosus (SLE). We previously identified elevated levels of oxidized low-density lipoprotein (OxLDL) together with elevated levels of autoantibodies related to OxLDL as risk factors for cardiovascular disease in female patients with SLE. Autoantibodies to OxLDL are common in SLE and cross-react with anticardiolipin antibodies (aCL). We therefore hypothesized that lipid peroxidation is enhanced in patients with SLE in general. METHODS: One hundred forty-seven female patients with SLE and 60 age- and sex-matched controls were compared. A monoclonal antibody to oxidized phospholipids, EO6, was used to determine oxidation epitopes on LDL. Anti-OxLDL and autoantibodies to malondialdehyde (MDA)-modified LDL, cardiolipin, and oxidized aCL were determined by chemiluminescence technique. RESULTS: As determined by binding of EO6, patients with SLE had a higher level of oxidized phospholipids on LDL (P = 0.005) compared with controls. The level of OxLDL (e.g., oxidized phospholipid/apolipoprotein B) was associated with arterial disease (P = 0.006) and renal manifestations (P = 0.04). As reported previously, levels of aCL, autoantibodies to OxLDL, and autoantibodies to MDA-modified LDL were enhanced and were closely correlated in SLE. Anticardiolipin antibodies from these SLE patients recognized mainly oxidized forms of cardiolipin, indicating that antigenic epitopes on cardiolipin are related to lipid peroxidation in patients with SLE. CONCLUSION: In general, patients with SLE (particularly those with cardiovascular disease) had more oxidized epitopes on LDL compared with controls. Furthermore, aCL in these patients recognized epitopes generated during lipid peroxidation. Thus, "neo" self antigens on lipoproteins, generated during oxidation, are present in SLE and may be of importance for the development of premature cardiovascular disease and possibly also for other autoimmune phenomena observed in SLE.

Adult↗

Decreased binding of annexin v to endothelial cells: a potential mechanism in atherothrombosis of patients with systemic lupus erythematosus.

OBJECTIVE: The cause of the exceedingly high risk of atherothrombosis in systemic lupus erythematosus (SLE) is not clear but antiphospholipid antibodies (aPL) and potentially antithrombotic annexin V have been implicated. METHODS AND RESULTS: Twenty-six women (52+/-8.2 years) with SLE and a history of cardiovascular disease (CVD) (SLE cases) were compared with 26 women with SLE but no CVD (SLE controls) and 26 healthy women (population controls). Common carotid intima-media thickness (IMT) was determined by B-mode ultrasound as a surrogate measure of atherosclerosis. Annexin V binding to human umbilical vein endothelial cells (HUVECs) as determined by flow cytometry after 24-hour culture with plasma was decreased when plasma from SLE cases was used (SLE cases versus population controls: P=0.002; SLE cases versus SLE controls P=0.02). Antibodies against cardiolipin were among IgG antibodies causing decreased binding. There was a positive association between annexin V binding and IMT (R=0.73; P<0.001) among SLE cases. Immunohistochemical analysis revealed presence of annexin V in all human atherosclerotic plaques tested, especially at sites prone to rupture. CONCLUSIONS: Decreased annexin V binding to endothelium caused by antibodies may represent a novel mechanism of atherothrombosis. We hypothesize that even though annexin V may promote plaque growth at some disease stages, it may also stabilize plaque.

Annexin A5↗

Platelet-activating factor-acetylhydrolase and other novel risk and protective factors for cardiovascular disease in systemic lupus erythematosus.

OBJECTIVE: There is an important inflammatory component to atherosclerosis and cardiovascular disease (CVD). It is therefore interesting that the risk of CVD is high in inflammatory diseases such as systemic lupus erythematosus (SLE). In this study, we investigated nontraditional risk factors for the development of CVD in patients with SLE. METHODS: Twenty-six women (mean age 52 years) with SLE and a history of CVD were compared with 26 age-matched women with SLE and no clinical manifestations of CVD (SLE controls) and 26 age-matched healthy women (population controls). Serum levels of several novel nontraditional risk and protective factors were determined: heat-shock protein (HSP)-related factors (Hsp60, Hsp70, anti-human Hsp60, anti-human Hsp70, and anti-mycobacterial Hsp65), platelet-activating factor-acetylhydrolase (PAF-AH) activity, secretory phospholipase A(2) GIIA (sPLA(2)), and anti-endothelial cell antibody (AECA). The intima-media thickness and the presence of plaques in the common carotid arteries were determined by B-mode ultrasound as a surrogate measure of atherosclerosis. RESULTS: Levels of PAF-AH, but not HSP-related factors, AECA, or sPLA(2), were significantly increased in SLE cases. Only PAF-AH discriminated between SLE cases and SLE controls (P = 0.005). PAF-AH was significantly associated with low-density lipoprotein (LDL) cholesterol and total cholesterol in the SLE cases (r = 0.50, P = 0.0093 and r = 0.54, P = 0.0045), but not in either control group. CONCLUSION: The increased levels of PAF-AH in SLE cases and the association between PAF-AH and LDL cholesterol adds support to the notion that PAF-AH may promote atherothrombosis in SLE. The role of HSPs in CVD is complex, since anti-Hsp65 appears to be associated with the presence of CVD, whereas Hsp70 might protect against it. In this cross-sectional study, levels of HSP-related factors, AECA, and sPLA(2) were not associated with CVD in SLE.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

The A-1087IL-10 allele is associated with cardiovascular disease in SLE.

The risk of cardiovascular disease (CVD) in SLE patients is very high. It is therefore surprising that IL-10 has been discussed both as pathogenic in SLE and as an atheroprotective cytokine. In contrast, TNF is believed to be atherogenic and we recently reported that raised activity in the TNF-system is implicated in SLE-related CVD. Twenty-six (aged 52 +/- 8 years) female patients with SLE and a history of CVD (myocardial infarction, angina, stroke or claudication) were compared with 26 age-matched SLE patients without CVD (SLE controls) or 26 age-matched population controls. The -1087IL-10 gene polymorphism was determined by PCR with restriction endonuclease mapping. Serum IL-10 and TNF-levels were determined by ELISA. The A allele frequency of -1087IL-10 gene in SLE/CVD was higher than in SLE controls (0.62 versus 0.42, p < 0.05). Ten (38%) of 26 SLE/CVD exhibited IL-10 AA genotype compared with five (19%) of 26 SLE controls. Serum IL-10 and TNF-levels were raised in SLE/CVD compared with SLE controls or population controls (p < 0.001). Furthermore, in SLE/CVD, a significantly reduced IL-10:TNF ratio was observed in patients with IL-10 AA genotype compared with AG or GG genotype (0.56 versus 0.77 versus 1.24, p < 0.05). In SLE controls and population controls, individuals with IL-10 GG genotype tended to have higher IL-10:TNF ratio. In conclusion, the A-1087IL-10 allele which has been reported to cause a lower capacity for IL-10 production could contribute to CVD in SLE. Furthermore, the IL-10 AA genotype is associated with reduced ratio of atheroprotective to atherogenic cytokines in SLE patients with CVD.

Alleles↗

Association of hypo-responsive toll-like receptor 4 variants with risk of myocardial infarction.

AIM: Toll-like receptor 4 (TLR4) is a receptor for bacterial lipopolysaccharide (LPS) and heat shock protein essential for innate immunity. Recent studies imply that TLR4 polymorphisms might affect atherogenesis. In this study we investigated the impact of LPS-hypo-responsive TLR4 variants on the risk of myocardial infarction (MI). METHODS AND RESULTS: Using TaqMan PCR technology, we determined the prevalence of the Asp299Gly and Thr399Ile polymorphisms in the TLR4 gene, and their association with MI in a study of 1213 survivors of a first MI and 1561 controls from the Stockholm region. The frequency was 0.096 for carriers of both 299Gly and 399Ile, and 0.006 for carriers of 399Ile alone. Carriers of both 299Gly and 399Ile were more frequent among the male cases than the male controls (10.7% vs 7.9%, p = 0.004). Compared with wild-type carriers, men with the 299Gly and the 399Ile TLR4 genotype had an increased risk of MI (OR [95% CI]: 1.4 [1.0;1.9]) whereas no association was observed for women. Furthermore a synergistic interaction was found between the TLR4 polymorphism and smoking in men. CONCLUSION: The association found between TLR4 genotype and risk of MI suggests that TLR4 genetic variants could potentially affect the susceptibility to MI and that TLR4-mediated innate immunity is implicated in the pathogenesis of MI.

Aged↗

Serum heat shock protein 70 levels predict the development of atherosclerosis in subjects with established hypertension.

Although heat shock proteins (Hsp's) are present in the sera of healthy individuals and at elevated levels in subjects with early cardiovascular disease, their physiologic role in and value for predicting the development and/or progression of atherosclerosis have not been evaluated. Serum was obtained from 218 subjects with established hypertension (diastolic pressure >95 mm Hg) before their enrollment in the European Lacidipine Study on Atherosclerosis. Hsp60 and Hsp70, and anti-human Hsp60, anti-human Hsp70, and anti-mycobacterial Hsp65 antibody levels were measured by enzyme immunoassay. As an indicator of the presence/progression of atherosclerosis, the means of the maximum intima-media (I-M) thicknesses in the far walls of common carotid arteries and bifurcations (CBMmax) were determined by ultrasonography at the time of enrollment and 4 years afterward. Increases in I-M thicknesses at follow-up were less prevalent in subjects having high serum Hsp70 levels (75th percentile) at the time of enrollment (odds ratio, 0.42; 95% confidence interval [CI], 0.22 to 0.8, P=0.008). Although a similar trend was observed for serum Hsp60 levels, this was not statistically significant (odds ratio, 0.6; 95% CI, 0.32 to 1.11, P=0.10). There was no relation between anti-Hsp antibody levels and changes in I-M thicknesses. The relation between Hsp70 levels and changes in I-M thickness was independent of age, atenolol or lacidipine treatment, smoking habits, and blood lipid levels. These findings indicate that circulating Hsp70 levels predict the development of atherosclerosis in subjects with established hypertension, and an intriguing possibility is that Hsp70 protects against or modifies the progression of atherosclerosis in this subject group.

Arteriosclerosis↗

Elevated triglycerides and low levels of high-density lipoprotein as markers of disease activity in association with up-regulation of the tumor necrosis factor alpha/tumor necrosis factor receptor system in systemic lupus erythematosus.

OBJECTIVE: To investigate how blood lipid levels are related to disease activity, clinical characteristics, and serum levels of tumor necrosis factor alpha (TNF alpha) and its soluble type 1 and 2 receptors, sTNFR1 and sTNFR2, in systemic lupus erythematosus (SLE). METHODS: Fasting blood samples were obtained from an unselected cohort of SLE patients at Karolinska Hospital (n = 208, mean +/- SD age 45.7 +/- 14.2 years). Disease activity was estimated using the SLE Disease Activity Measure (SLAM). Levels of circulating TNF alpha, sTNFR1, and sTNFR2 were determined by enzyme-linked immunosorbent assay. Blood lipid levels obtained after overnight fasting were analyzed by routine chemistry. RESULTS: Triglyceride (TG) levels were associated with the SLAM score (r = 0.48, P < 0.0001) and with the activities of TNF alpha (r = 0.29, P = 0.0001), sTNFR1 (r = 0.38, P < 0.0001), and sTNFR2 (r = 0.40, P < 0.0001). High-density lipoprotein (HDL) levels were negatively associated with the SLAM score (r = -0.27, P = 0.0003) and with the activities of TNF alpha (r = -0.15, P = 0.04) and sTNFR2 (r = -0.19, P = 0.01). High levels of TGs, total cholesterol, TNF alpha, sTNFR1, and sTNFR2 all showed close correlations with the presence of nephritis and arterial disease (P < 0.05). In multiple logistic regression models, the TNF alpha activity and TG levels were independent determinants (P = 0.003 for both) of active disease (SLAM score > or =7). CONCLUSION: Dyslipoproteinemia with high TG/low HDL levels correlates with disease activity in SLE, and enhanced activity in the TNFalpha/sTNFR system seems to be an important underlying factor. Both dyslipoproteinemia and enhanced activity of the TNF alpha system are closely related to cardiovascular and renal manifestations in SLE, and thus both may serve as markers of more severe disease.

Adult↗

Interleukin-6 serum levels and genotypes influence the risk for myocardial infarction.

OBJECTIVE: Several studies show that the inflammatory component in atherosclerosis may contribute to increased risk for cardiovascular disease (CVD). Interleukin-6 (IL-6) is a key pro-inflammatory and immune-stimulatory cytokine of presumed importance for CVD and the metabolic syndrome. METHODS AND RESULTS: In this case-control study, 1179 surviving myocardial infarction (MI) cases and 1528 healthy controls were genotyped for three IL-6 promoter SNPs, and serum concentrations of IL-6 and C-reactive protein (CRP) were measured. In men, MI risk assessed as odds ratios (OR) was higher with increasing IL-6 levels, with the highest compared to the lowest IL-6 quartiles giving an OR of 2.7 [95% CI 1.7-4.4]. The ORs were independent from the effects of elevated CRP which were associated with modest MI risks (OR = 1.6 [95% CI 1.0-2.5]). Also, synergistic interactions between high IL-6 levels and hypercholesterolaemia further increased MI risk estimates. The -174C allele was associated with lower serum-insulin levels among male controls but did not significantly influence MI risk or IL-6 levels. CONCLUSIONS: Elevated IL-6 levels are important risk markers for MI in men, the risk being further enhanced through synergistic interaction with hypercholesterolaemia. The data provide no clear evidence that polymorphisms in the IL-6 promotor region play a significant role in the pathogenesis of MI, and it remains to be further evaluated whether or not the -174C allele is of relevance for insulin resistance.

C-Reactive Protein↗

Risk factors for cardiovascular disease in patients with periodontitis.

AIMS: This study compared plasma levels of established risk markers for atherosclerosis and indices of inflammation in 50 patients with severe periodontitis to those in 46 healthy cases. METHODS AND RESULTS: Full blood counts were performed and levels of high density lipoproteins (HDL), total cholesterol, haptoglobin, elastase, C-reactive protein (CRP), IL-6, TNFalpha receptor-1, alpha-1-antitrypsin and antibodies against human heat shock protein (Hsp) 60, mycobacterial Hsp65 and oxLDL were determined. Total cholesterol levels were similar in both groups, whereas HDL levels were lower (P=0.007) and the lipid profile (total cholesterol/HDL) was consequentially higher (P=0.03) in patients. Monocyte counts were elevated (0.56 vs 0.44x10(9)/l; P=0.002) and CRP levels were higher in patients, but TNFalpha receptor-1 and elastase levels were not. Anti-oxLDL antibody levels were similar, as were levels of haptoglobin, IgG anti HSP60, IgA and IgG anti-Hsp65 antibodies. Levels of IgA anti-Hsp60 antibodies were lower in patients (P=0.0001). Logistic regression analysis revealed a relationship between periodontitis and HDL (OR 2.15/0.5mmol/l, P=0.02) and body mass index (OR 4.54 P=0.005). CONCLUSIONS: Serological differences in subjects with periodontitis, some of which involve established risk factors for atherosclerosis, might provide insight into the reported epidemiological association between periodontitis and cardiovascular disease.

Adult↗

Oxidised LDL modulates immune-activation by an IL-12 dependent mechanism.

Oxidised low density lipoprotein (oxLDL) is one factor that may cause the immune reaction in the artery wall characteristic of atherosclerosis. OxLDL can promote immune activation as determined by enhanced secretion of IFN-gamma and TNF by immune competent cells. We previously demonstrated that Platelet-activating factor (PAF)-like lipids and/or lysophosphatidylcholine (LPC) in OxLDL contribute significantly to this immune activation, but these factors may also inhibit immune activation, at higher concentrations. We here demonstrate that IL-12 induces enhanced IFN-gamma secretion in peripheral blood mononuclear cells (PBMC), with no addition of a specific antigen, as determined by ELISPOT. Antibodies to IL-12 and to MHC class II inhibited both IL-12- and oxLDL-induced IFN-gamma secretion. OxLDL induced IL-12 production in PBMC. In the presence of IL-10, a T helper 2 cytokine, oxLDL induced a decreased IFN-gamma secretion, indicating that the local cytokine-milieu may determine the immunological properties of oxLDL. IL-10 could also be induced by OxLDL. Mononuclear leukocytes were prepared directly from human atherosclerotic plaques obtained at carotid operations. OxLDL had the capacity to induce IL-12, IL-10 and TNF from plaque cells using ELISPOT. Taken together, our data indicate that oxLDL can modulate immune reactivity in atherosclerosis by a nonspecific mechanism. OxLDL can be inhibitory, especially at higher concentrations. However, oxLDL can also promote immune activation by functioning as an adjuvant, potentiating and/or modulating immune-reactions via IL-12 and other cytokines including IL-10. This suggests that a specific T cell epitope in oxLDL is not necessary for oxLDL-induced T cell activation.

Adjuvants, Immunologic↗