Inflammatory F2-isoprostane, prostaglandin F2α, pentraxin 3 levels and breast cancer risk: The Swedish Mammography Cohort.

INTRODUCTION: Breast cancer is a common cancer among women. Identifying cellular participation of F2-isoprostane, prostaglandin F2α (PGF2α) and pentraxin 3 (PTX3) in cancer we evaluated whether their prediagnostic systemic levels that originate from different inflammatory pathways were associated with breast cancer risk. METHODS: Seventy-eight breast cancer cases diagnosed after blood collection and 797 controls from the Swedish Mammography Cohort were analysed for urinary F2-isoprostane, PGF2α and plasma PTX3 levels. RESULTS: None of the biomarkers investigated were significantly associated with breast cancer risk. However, there was the suggestion of an inverse association with PTX3 with multivariable adjusted ORs (95% CI) of 0.56 (95% CI=0.29-1.06) and 0.67 (95% CI=0.35-1.28) for the second and third tertiles, respectively (ptrend=0.20). No associations were observed between F2-isoprostane (OR=0.87; 95% CI=0.48-1.57; ptrend=0.67) and PGF2α metabolite (OR=1.03; 95% CI=0.56-1.88; ptrend=0.91) comparing the top to bottom tertiles. CONCLUSIONS: The systemic levels of F2-isoprostane, PGF2α and PTX3 witnessed in women who later developed breast cancer may not provide prognostic information regarding tumor development in spite of their known involvement in situ cellular context. These observations may indicate that other mechanisms exist in controlling cellular formation of F2-isoprostane, PGF2α and PTX3 and their systemic availability in breast cancer patients.

Soluble vascular endothelial growth factor receptors 2 (sVEGFR-2) and 3 (sVEGFR-3) and breast cancer risk in the Swedish Mammography Cohort.

Vascular endothelial growth factor (VEGF) is a signalling protein that has been established as a contributor to tumor angiogenesis, and expression of VEGF and its soluble receptors (sVEGFR2 and sVEGFR3) have been demonstrated in breast cancer cells. However, no prospective studies have examined the association between prediagnostic sVEGFR levels and breast cancer risk. We conducted a prospective case-control study nested within the Swedish Mammography Cohort examining the association between sVEGFR2 and 3 levels and breast cancer risk. The analysis included 69 incident breast cancer cases diagnosed after blood collection and 719 controls. Logistic regression models were used to calculate odds ratios and 95% confidence intervals. After adjustment for breast cancer risk factors, sVEGFR2 levels were associated with breast cancer risk (OR=1.28; 95% CI=1.06-1.56 per 1000 ng/L increase in concentration) while sVEGFR3 levels were not related to such risk (OR=1.00; 95% CI=0.93-1.07). Our results suggest that sVEGFR2 levels may be positively associated with breast cancer risk, however future studies with larger case groups are necessary to confirm this association.

Cellular Expression of Cyclooxygenase, Aromatase, Adipokines, Inflammation and Cell Proliferation Markers in Breast Cancer Specimen.

Current evidences suggest that expression of Ki67, cyclooxygenase (COX), aromatase, adipokines, prostaglandins, free radicals, ß-catenin and α-SMA might be involved in breast cancer pathogenesis. The main objective of this study was to compare expression/localization of these potential compounds in breast cancer tissues with tissues collected adjacent to the tumor using immunohistochemistry and correlated with clinical pathology. The breast cancer specimens were collected from 30 women aged between 49 and 89 years who underwent breast surgery following cancer diagnosis. Expression levels of molecules by different stainings were graded as a score on a scale based upon staining intensity and proportion of positive cells/area or individually. AdipoR1, adiponectin, Ob-R, leptin, COX-1, COX-2, aromatase, PGF2α, F2-isoprostanes and α-SMA were localised on higher levels in the breast tissues adjacent to the tumor compared to tumor specimens when considering either score or staining area whereas COX-2 and AdipoR2 were found to be higher considering staining intensity and Ki67 on score level in the tumor tissue. There was no significant difference observed on ß-catenin either on score nor on staining area and intensity between tissues adjacent to the tumor and tumor tissues. A positive correlation was found between COX-1 and COX-2 in the tumor tissues. In conclusion, these suggest that Ki67, COXs, aromatase, prostaglandin, free radicals, adipokines, ß-catenin and α-SMA are involved in breast cancer. These further focus the need of examination of tissues adjacent to tumor, tumor itself and compare them with normal or benign breast tissues for a better understanding of breast cancer pathology and future evaluation of therapeutic benefit.

Is There Any Role for Serum Cathepsin S and CRP Levels on Prognostic Information in Breast Cancer? The Swedish Mammography Cohort.

Breast cancer is the most common cancer among women, and both low-grade inflammation and cathepsins might have important roles in breast cancer. We questioned whether prediagnostic circulating levels of C-reactive protein (CRP), cathepsin B, and cathepsin S were associated with breast cancer risk. Sixty-nine incident breast cancer cases diagnosed after blood collection and 719 controls from the Swedish Mammography Cohort were analyzed for systemic CRP, cathepsin B, and cathepsin S. Cathepsin S and inflammation (high-sensitivity CRP [hsCRP])-adjusted cathepsin S were inversely associated with breast cancer risk (cathepsin S: odds ratio [OR] for top vs. bottom tertile=0.46; 95% confidence interval [CI]=0.23-0.92; p(trend)=0.02; hsCRP-adjusted cathepsin S: OR of 0.44; 95% CI=0.22-0.87; p(trend)=0.02). hsCRP was significantly associated with increased breast cancer risk (OR for top vs. bottom tertile=2.01; 95% CI=1.02-3.95; p(trend)=0.04). No significant association was observed between cathepsin B and breast cancer risk (OR for top vs. bottom tertile=0.67; 95% CI=0.32-1.40; ptrend=0.30). These observations lead to the hypothesis that levels of cathepsin S and hsCRP observed in women who later developed breast cancer may provide prognostic information regarding tumor development and need to be evaluated in prospective studies.

Biomarkers of oxidative stress study VI. Endogenous plasma antioxidants fail as useful biomarkers of endotoxin-induced oxidative stress.

This is the newest report in a series of publications aiming to identify a blood-based antioxidant biomarker that could serve as an in vivo indicator of oxidative stress. The goal of the study was to test whether acutely exposing Göttingen mini pigs to the endotoxin lipopolysaccharide (LPS) results in a loss of antioxidants from plasma. We set as a criterion that a significant effect should be measured in plasma and seen at both doses and at more than one time point. Animals were injected with two doses of LPS at 2.5 and 5 µg/kg iv. Control plasma was collected from each animal before the LPS injection. After the LPS injection, plasma samples were collected at 2, 16, 48, and 72 h. Compared with the controls at the same time point, statistically significant losses were not found for either dose at multiple time points in any of the following potential markers: ascorbic acid, tocopherols (α, δ, γ), ratios of GSH/GSSG and cysteine/cystine, mixed disulfides, and total antioxidant capacity. However, uric acid, total GSH, and total Cys were significantly increased, probably because LPS had a harmful effect on the liver. The leakage of substances from damaged cells into the plasma may have increased plasma antioxidant concentrations, making changes difficult to interpret. Although this study used a mini-pig animal model of LPS-induced oxidative stress, it confirmed our previous findings in different rat models that measurement of antioxidants in plasma is not useful for the assessment of oxidative damage in vivo.

Prostaglandin F2α formation is associated with mortality in a Swedish community-based cohort of older males.

AIMS: An increasing number of clinical studies highlight the importance of the inflammatory mediator prostaglandin F2 α (PGF(2α)). Prostaglandin F2 α activity has been suggested to play pivotal roles in the development of cardiovascular diseases and cancer. However, whether systemic PGF(2α) concentrations may signal mortality is unknown. The aim was to evaluate in vivo PGF(2α) formation, by measuring urinary 15-keto-dihydro-PGF(2α), and mortality risk in a community setting. METHODS AND RESULTS: Urinary 15-keto-dihydro-PGF(2α) was measured in a Swedish population of 670 men (aged 77-78 years) and the participants were followed up for a median of 9.7 years (383 died, among them 156 of cardiovascular causes and 102 of cancer). In Cox regression models, urinary 15-keto-dihydro-PGF(2α) was significantly associated with cardiovascular mortality [multivariate hazard ratio (HR) for 1 SD increase of urinary 15-keto-dihydro-PGF(2α): 1.18; 95% CI:1.04-1.34; P = 0.01) independent of established cardiovascular risk factors including C-reactive protein. Urinary 15-keto-dihydro-PGF(2α) was also independently associated with total mortality (multivariate HR for 1 SD increase of urinary 15-keto-dihydro-PGF(2α): 1.11; 95% CI: 1.01-1.21; P = 0.03). The combination of 15-keto-dihydro-PGF(2α) concentrations above the median and high serum high-sensitive C-reactive protein (>3 mg/L) was independently associated with a two-fold increased risk of cancer and total mortality (P = 0.02 and P < 0.001, respectively). CONCLUSION: This is the first study to show that the inflammatory mediator PGF(2α) was independently associated with mortality and specifically cardiovascular mortality 10 years later. The results are in line with the emerging evidence of the importance of the inflammatory mediator PGF(2α) in fatal cardiovascular disease.

Primary osteosarcoma of breast, a rare case.

Mammary sarcomas are very uncommon and make up less than 1% of all primary breast malignancies.Primary osteosarcoma of the breast is extremely rare and represents 12.5% of mammary sarcomas. A secondary lesion from a primary osteosarcoma of the bone should be considered in the differential diagnosis. In addition, the absence of a direct connection between the tumour and the underlying skeleton is mandatory for the diagnosis.We report a case of primary osteosarcoma of the breast occurring in young patient with fatal evolution.

Involvement of inflammation in normal pregnancy.

To study the role of inflammation throughout normal pregnancy and postpartum, 37 women with normal pregnancies, including normal neonatal outcome, participated. Blood and urine samples were collected from each woman at least six times during pregnancy and postpartum. Plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and urinary levels of a prostaglandin-F2α (PGF2α ) metabolite were measured. Median, 25th to 75th centile and average change per gestational week of IL-6, TNF-α and the PGF2α metabolite were measured. Levels of IL-6 increased significantly throughout pregnancy and remained high postpartum. No change in TNF-α could be seen. The PGF2α metabolite levels increased significantly throughout pregnancy and decreased postpartum. These results suggest that mild but significant inflammatory activity is involved in the development of normal pregnancy, which might have important physiological roles.

Targeting oxidative injury and cytokines' activity in the treatment with anti-tumor necrosis factor-α antibody for complex regional pain syndrome 1.

Cytokines and oxygen free radicals have been implicated in the potential pathogenic development of complex regional pain syndrome (CRPS). We aimed to analyze the relationship between clinical status, circulating levels of cytokines, and markers of oxidative damage during the treatment with anti-TNFα antibodies. The patient chosen for treatment had not had improvement through a number of conventional therapies and fulfilled the current diagnostic criteria for CRPS-1. We investigated the clinical variables before and after systemic administration of 1.4 mg/kg anti-TNFα antibody (infliximab), repeated after 1 month in a dose of 3 mg/kg. Blood samples were collected before and after anti-TNFα antibodies administration, and plasma was analyzed for 8-isoprostane-prostaglandin F2α (8-iso-PGF2α, a marker of oxidative injury) and cytokines (TNF-α, IL-4, IL-6, IL-7, IL-8, IL-10, IL-17A). Plasma concentrations of 8-iso-PGF2α were measured with radioimmunoassay (RIA), and the kinetics of cytokines were detected in plasma by antibody-based proximity ligation (PLA). Pathologically high levels of 8-iso-PGF2α were found in the patient. Immediately after each administration of infliximab, the levels of 8-iso-PGF2α decreased. Although the patient showed an improvement of the cutaneous dystrophic symptoms and diminished pain associated with these lesions, the levels of circulating TNFα increased after the administration of anti-TNFα antibodies. In a patient with CRPS-1 treated with anti-TNFα antibodies, we report increased levels of circulating TNFα and a temporary mitigation of oxidative stress as measured by plasma F2 -isoprostane. This case report provides evidence 2 supporting the indication of monitoring the oxidative stress biomarkers during treatment with anti-TNFα antibodies in CRPS 1.

Eicosanoids and adipokines in breast cancer: from molecular mechanisms to clinical considerations.

Chronic inflammation is one of the foremost risk factors for different types of malignancies, including breast cancer. Additional risk factors of this pathology in postmenopausal women are weight gain, obesity, estrogen secretion, and an imbalance in the production of adipokines, such as leptin and adiponectin. Various signaling products of transcription factor, nuclear factor-kappaB, in particular inflammatory eicosanoids, reactive oxygen species (ROS), and cytokines, are thought to be involved in chronic inflammation-induced cancer. Together, these key components have an influence on inflammatory reactions in malignant tissue damage when their levels are deregulated endogenously. Prostaglandins (PGs) are well recognized in inflammation and cancer, and they are solely biosynthesized through cyclooxygenases (COXs) from arachidonic acid. Concurrently, ROS give rise to bioactive isoprostanes from arachidonic acid precursors that are also involved in acute and chronic inflammation, but their specific characteristics in breast cancer are less demonstrated. Higher aromatase activity, a cytochrome P-450 enzyme, is intimately connected to tumor growth in the breast through estrogen synthesis, and is interrelated to COXs that catalyze the formation of both inflammatory and anti-inflammatory PGs such as PGE(2), PGF(2α), PGD(2), and PGJ(2) synchronously under the influence of specific mediators and downstream enzymes. Some of the latter compounds upsurge the intracellular cyclic adenosine monophosphate concentration and appear to be associated with estrogen synthesis. This review discusses the role of COX- and ROS-catalyzed eicosanoids and adipokines in breast cancer, and therefore ranges from their molecular mechanisms to clinical aspects to understand the impact of inflammation.

Acetylsalicylic acid treatment until surgery reduces oxidative stress and inflammation in patients undergoing coronary artery bypass grafting.

OBJECTIVES: Acetylsalicylic acid (ASA) is a cornerstone in the treatment of coronary artery disease (CAD) due to its antiplatelet effect. Cessation of aspirin before coronary artery bypass grafting (CABG) is often recommended to avoid bleeding, but the practice is controversial because it is suggested to worsen the underlying CAD. The aims of the present prospective, randomized study were to assess if ASA administration until the day before CABG decreases the oxidative load through a reduction of inflammation and myocardial damage, compared with patients with preoperative discontinuation of ASA. METHODS: Twenty patients scheduled for CABG were randomly assigned to either routine ASA-treatment (160 mg daily) until the time of surgery (ASA), or to ASA-withdrawal 7 days before surgery (No-ASA). Blood-samples were taken from a radial artery and coronary sinus, during and after surgery and analysed for 8-iso-prostaglandin (PG) F2α; a major F2-isoprostane, high-sensitivity C-reactive protein (hs-CRP), cytokines and troponin T. Left ventricle Tru-Cut biopsies were taken from viable myocardium close to the left anterior descending artery just after connection to cardiopulmonary bypass, and before cardioplegia were established for gene analysis (Illumina HT-12) and immunohistochemistry (CD45). RESULTS: 8-Iso-PGF2α at baseline (t1) were 111 (277) pmol/l and 221 (490) pmol/l for ASA and No-ASA, respectively (P = 0.065). Area under the curve showed a significantly lower level in plasma concentration of 8-iso-PGF2α and hsCRP in the ASA group compared with the No-ASA group with (158 pM vs 297 pM, P = 0.035) and hsCRP (8.4 mg/l vs 10.1 mg/l, P = 0.013). All cytokines increased during surgery, but no significant differences between the two groups were observed. Nine genes (10 transcripts) were found with a false discovery rate (FDR) <0.1 between the ASA and No-ASA groups. CONCLUSIONS: Continued ASA treatment until the time of CABG reduced oxidative and inflammatory responses. Also, a likely beneficial effect upon myocardial injury was noticed. Although none of the genes known to be involved in oxidative stress or inflammation took a different expression in myocardial tissue, the genetic analysis showed interesting differences in the mRNA level. Further research in this field is necessary to understand the role of the genes.

Effects of enriched environment on COX-2, leptin and eicosanoids in a mouse model of breast cancer.

Cyclooxygenase-2 (COX-2) and adipokines have been implicated in breast cancer. This study investigated a possible link between COX-2 and adipokines in the development of mammary tumors. A model of environmental enrichment (EE), known to reduce tumor growth was used for a syngeneic murine model of mammary carcinoma. 3-week-old, female C57BL/6 mice were housed in standard environment (SE) or EE cages for 9 weeks and transplanted orthotopically with syngeneic EO771 adenocarcinoma cells into the right inguinal mammary fat pad. EE housing influenced mammary gland development with a decrease in COX-2 expressing cells and enhanced side-branching and advanced development of alveolar structures of the mammary gland. Tumor volume and weight were decreased in EE housed mice and were associated with a reduction in COX-2 and Ki67 levels, and an increase in caspase-3 levels. In tumors of SE mice, high COX-2 expression correlated with enhanced leptin detection. Non-tumor-bearing EE mice showed a significant increase in adiponectin levels but no change in those of leptin, F(2)-isoprostanes, PGF(2α), IL-6, TNF-α, PAI-1, and MCP-1 levels. Both tumor-bearing groups (SE and EE housing) had increased resistin, IL-6, TNF-α, PAI-1 and MCP-1 levels irrespective of the different housing environment demonstrating higher inflammatory response due to the presence of the tumor. This study demonstrates that EE housing influenced normal mammary gland development and inhibited mammary tumor growth resulting in a marked decrease in intratumoral COX-2 activity and an increase in the plasma ratio of adiponectin/leptin levels.

Inflammation, oxidative stress, glomerular filtration rate, and albuminuria in elderly men: a cross-sectional study.

BACKGROUND: The role of inflammation and oxidative stress in mild renal impairment in the elderly is not well studied. Accordingly, we aimed at investigating the associations between estimated glomerular filtration rate (eGFR), albumin/creatinine ratio (ACR), and markers of different inflammatory pathways and oxidative stress in a community based cohort of elderly men. FINDINGS: Cystatin C-based GFR, ACR, and biomarkers of cytokine-mediated inflammation (interleukin-6, high-sensitivity C-reactive protein[CRP], serum amyloid A[SAA]), cyclooxygenase-mediated inflammation (urinary prostaglandin F2α [PGF2α]), and oxidative stress (urinary F2 isoprostanes) were assessed in the Uppsala Longitudinal Study of Adult Men(n = 647, mean age 77 years). RESULTS: In linear regression models adjusting for age, BMI, smoking, blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides, and treatment with statins, ACE-inhibitors, ASA, and anti-inflammatory agents, eGFR was inversely associated with CRP, interleukin-6, and SAA (ß-coefficient -0.13 to -0.19, p < 0.001 for all), and positively associated with urinary F2-isoprostanes (ß-coefficient 0.09, p = 0.02). In line with this, ACR was positively associated with CRP, interleukin-6, and SAA (ß- coefficient 0.09-0.12, p < 0.02 for all), and negatively associated with urinary F2-isoprostanes (ß-coefficient -0.12, p = 0.002). The associations were similar but with lower regression coefficients in a sub-sample with normal eGFR (>60 ml/min/1.73 m2, n = 514), with the exception that F2-isoprostane and SAA were no longer associated with eGFR. CONCLUSION: Our data indicate that cytokine-mediated inflammation is involved in the early stages of impaired kidney function in the elderly, but that cyclooxygenase-mediated inflammation does not play a role at this stage. The unexpected association between higher eGFR/lower albuminuria and increased F2-isoprostanes in urine merits further studies.

Does consumption of two portions of salmon per week enhance the antioxidant defense system in pregnant women?

Salmon is a rich source of marine n-3 fatty acids, which may increase oxidative stress and, in turn, could affect the antioxidant defense system in blood plasma and erythrocytes of pregnant women. The Salmon in Pregnancy Study provided two meals of salmon per week to pregnant women from week 20 of gestation; the control group maintained their habitual diet low in oily fish. Higher selenium and retinol plasma concentrations were observed after dietary salmon supplementation. Besides, a concomitant increase in selenium and glutathione concentration as well as glutathione peroxidase and reductase activities were detected as pregnancy progressed. However, tocopherols, retinol, ß-carotene, and coenzyme Q(10) decreased in late pregnancy. Collectively, our findings lead to the hypothesis that increased farmed salmon intake may increase antioxidant defenses during pregnancy. Clinical trials identifier NCT00801502.

Effects of similar intakes of marine n-3 fatty acids from enriched food products and fish oil on cardiovascular risk markers in healthy human subjects.

There is convincing evidence that consumption of fish and fish oil rich in long-chain (LC) n-3 PUFA (n-3 LCPUFA), EPA (20 : 5n-3) and DHA (22 : 6n-3) reduce the risk of CHD. The aim of the present study was to investigate whether n-3 LCPUFA-enriched food products provide similar beneficial effects as fish oil with regard to incorporation into plasma lipids and effects on cardiovascular risk markers. A parallel 7-week intervention trial was performed where 159 healthy men and women were randomised to consume either 34 g fish pâté (n 44), 500 ml fruit juice (n 38) or three capsules of concentrated fish oil (n 40), all contributing to a daily intake of approximately 1 g EPA and DHA. A fourth group did not receive any supplementation or food product and served as controls (n 37). Plasma fatty acid composition, serum lipids, and markers of inflammation and oxidative stress were measured. Compared with the control group, plasma n-3 LCPUFA and EPA:arachidonic acid ratio increased equally in all intervention groups. However, no significant changes in blood lipids and markers of inflammation and oxidative stress were observed. In conclusion, enriched fish pâté and fruit juice represent suitable delivery systems for n-3 LCPUFA. However, although the dose given is known to reduce the risk of CVD, no significant changes were observed on cardiovascular risk markers in this healthy population.

Association between serum cathepsin S and mortality in older adults.

CONTEXT: Experimental data suggest that cathepsin S, a cysteine protease, is involved in the complex pathways leading to cardiovascular disease and cancer. However, prospective data concerning a potential association between circulating cathepsin S levels and mortality are lacking. OBJECTIVE: To investigate associations between circulating cathepsin S levels and mortality in 2 independent cohorts of elderly men and women. DESIGN, SETTING, AND PARTICIPANTS: Prospective study using 2 community-based cohorts, the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 1009; mean age: 71 years; baseline period: 1991-1995; median follow-up: 12.6 years; end of follow-up: 2006) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 987; 50% women; mean age: 70 years; baseline period: 2001-2004; median follow-up: 7.9 years; end of follow-up: 2010). Serum samples were used to measure cathepsin S. MAIN OUTCOME MEASURE: Total mortality. RESULTS: During follow-up, 413 participants died in the ULSAM cohort (incidence rate: 3.59/100 person-years at risk) and 100 participants died in the PIVUS cohort (incidence rate: 1.32/100 person-years at risk). In multivariable Cox regression models adjusted for age, systolic blood pressure, diabetes, smoking status, body mass index, total cholesterol, high-density lipoprotein cholesterol, antihypertensive treatment, lipid-lowering treatment, and history of cardiovascular disease, higher serum cathepsin S was associated with an increased risk for mortality (ULSAM cohort: hazard ratio [HR] for 1-unit increase of cathepsin S, 1.04 [95% CI, 1.01-1.06], P = .009; PIVUS cohort: HR for 1-unit increase of cathepsin S, 1.03 [95% CI, 1.00-1.07], P = .04). In the ULSAM cohort, serum cathepsin S also was associated with cardiovascular mortality (131 deaths; HR for quintile 5 vs quintiles 1-4, 1.62 [95% CI, 1.11-2.37]; P = .01) and cancer mortality (148 deaths; HR for 1-unit increase of cathepsin S, 1.05 [95% CI, 1.01-1.10]; P = .01). CONCLUSIONS: Among elderly individuals in 2 independent cohorts, higher serum cathepsin S levels were associated with increased mortality risk. Additional research is needed to delineate the role of cathepsin S and whether its measurement might have clinical utility.

Effect of industrially produced trans fat on markers of systemic inflammation: evidence from a randomized trial in women.

Consumption of industrially produced trans fatty acids (IP-TFA) has been positively associated with systemic markers of low-grade inflammation and endothelial dysfunction in cross-sectional studies, but results from intervention studies are inconclusive. Therefore, we conducted a 16 week double-blind parallel intervention study with the objective to examine the effect of IP-TFA intake on biomarkers of inflammation, oxidative stress, and endothelial dysfunction. Fifty-two healthy overweight postmenopausal women (49 completers) were randomly assigned to receive either partially hydrogenated soybean oil (15.7 g/day IP-TFA) or control oil without IP-TFA. After 16 weeks, IP-TFA intake increased baseline-adjusted serum tumor necrosis factor (TNF) α by 12% [95% confidence interval (CI): 5-20; P = 0.002] more in the IP-TFA group compared with controls. Plasma soluble TNF receptors 1 and 2 were also increased by IP-TFA [155 pg/ml (CI: 63-247); P < 0.001 and 480 pg/ml (CI: 72-887); P = 0.02, respectively]. Serum C-reactive protein, interleukin (IL) 6 and adiponectin and subcutaneous abdominal adipose tissue mRNA expression of IL6, IL8, TNFα, and adiponectin as well as ceramide content were not affected by IP-TFA, nor was urinary 8-iso-prostaglandin-F(2α). In conclusion, this dietary trial indicates that the mechanisms linking dietary IP-TFA to cardiovascular disease may involve activation of the TNFα system.

Obesity modifies the relations between serum markers of dairy fats and inflammation and oxidative stress among adolescents.

Pentadecanoic acid (15:0) and heptadecanoic acid (17:0), the dairy-specific saturated fatty acids have been inversely, while inflammation and oxidative stress have been positively related to the risk of cardiovascular disease (CVD). Both fatty acid metabolism and inflammation and oxidative stress may be influenced by adiposity. In the current cross-sectional analyses among adolescents (mean age 15 years), we determined whether overweight status modified the associations between dairy fatty acids (pentadecanoic acid (15:0) and heptadecanoic acid (17:0)) represented in serum phospholipids (PL) and markers of inflammation and oxidative stress. Six biomarkers for inflammation and oxidative stress were analyzed, including circulating adiponectin, C-reactive protein (CRP), cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and urinary 15-keto-dihydro-PGF2α (15-keto) and 8-iso-PGF2α (F2-iso). Generalized linear regression analyses, adjusted for age, gender, race, tanner score, total energy intake and physical activity, revealed that PL dairy fatty acids were inversely associated with CRP, F2-iso and 15-keto in overweight, but not in normal weight adolescents (all P(interaction) < 0.05). However, higher level of PL dairy fatty acids was associated with lower IL-6 among all adolescents. Further adjustment for dietary intake of calcium, vitamin D, protein, total flavonoids, and ω-3 fatty acids did not materially change the findings. Dairy-specific saturated fats, i.e., 15:0 and 17:0 fatty acids, may contribute to the potential health benefits of dairy products, especially for overweight adolescents.

A high intake of trans fatty acids has little effect on markers of inflammation and oxidative stress in humans.

Consumption of industrial trans fatty acids (iTFA) increases LDL cholesterol, decreases HDL cholesterol, and is strongly associated with a higher risk of cardiovascular disease (CVD). However, changes in circulating cholesterol cannot explain the entire effect. Therefore, we studied whether iTFA and conjugated linoleic acid (CLA) affect markers of inflammation and oxidative stress. Sixty-one healthy adults consumed each of 3 diets for 3 wk, in random order. Diets were identical except for 7% of energy provided by oleic acid (control diet), iTFA, or CLA. At the end of the 3 wk, we measured plasma inflammatory markers IL-6, C-reactive protein, tumor necrosis factor receptors I and II (TNF-RI and -RII), monocyte chemotactic protein-1 and E-selectin, and urinary 8-iso-PGF(2α), a marker of lipid peroxidation. Consumption of iTFA caused 4% lower TNF-RI concentrations and 6% higher E-selectin concentrations compared with oleic acid (control) and had no significant effect on other inflammatory markers. CLA did not significantly affect inflammatory markers. The urine concentration of 8-iso-PGF(2α) [geometric mean (95% CI)] was greater after the iTFA [0.54 (0.48, 0.60) nmol/mmol creatinine] and the CLA [1.2 (1.1, 1.3) nmol/mmol creatinine] diet periods than after the control period [0.45 (0.41, 0.50) nmol/mmol creatinine; P < 0.05]. In conclusion, high intakes of iTFA and CLA did not substantially affect plasma concentrations of inflammatory markers, but they increased the urine 8-iso-PGF(2α) concentration. However, it is unlikely this plays a major role in the mechanism by which iTFA increase the risk of CVD. However, more research is needed to fully understand the implications of these findings.