Leukotriene B4 limits the effectiveness of fish oil in an animal model of asthma.

This study aimed to evaluate the levels of eicosanoids derived from arachidonic acid (ARA) in the lungs of asthmatic rats supplemented with fish oil. The present data gives insight into the action of fish oil in asthma, related to its inability to modify the contractile capacity of tracheal smooth muscle reported previously in a model of asthma in rats. Male Wistar rats were supplemented daily with 1 g of fish oil/kg of body weight for 21 days. They were exposed to ovalbumin (OVA) after previous sensitization with OVA to induce asthma. Pulmonary levels of five eicosanoids were measured using immunoassay kits: PGE2, TXB2, LTB4, LXA4, and 8-iso PGF2α. In asthmatic rats, supplementation with fish oil resulted in lower concentrations of lung eicosanoids produced by cyclooxygenase-2 and 15-lipoxygenase: PGE2, TXB2, and LXA4, respectively. Fish oil supplementation also decreased the non-enzymatically produced eicosanoid 8-iso PGF2α. Fish oil supplementation did not affect LTB4, a metabolite of 5-lipoxygenase. The limited efficacy of fish oil supplementation in asthmatic rats is associated with a lack of action in reducing the levels of LTB4 in the lungs. Thus, fish oil differentially modulates the concentrations of eicosanoids derived from ARA via specific pathways in an animal model of asthma.

Genetically modified plants are an alternative to oily fish for providing n-3 polyunsaturated fatty acids in the human diet: A summary of the findings of a Biotechnology and Biological Sciences Research Council funded project.

The n-3 polyunsaturated fatty acids (PUFA) present primarily in oily fish, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are important components of cell membranes and that are needed for normal development and cell function. Humans have very limited capacity for EPA and DHA synthesis from α-linolenic acid and so they must be obtained pre-formed from the diet. However, perceived unpalatability of oily fish and fish oil concerns about contamination with environmental pollutants, dietary choices that exclude fish and animal products, and price limit the effectiveness of recommendations for EPA and DHA intakes. Moreover, marine sources of EPA and DHA are diminishing in the face of increasing demands. Therefore, an alternative source of EPA and DHA is needed that is broadly acceptable, can be upscaled and is sustainable. This review discusses these challenges and, using findings from recent nutritional trials, explains how they may be overcome by seed oils from transgenic plants engineered to produce EPA and DHA. Trials in healthy men and women assessed the acute uptake and appearance in blood over 8 hours of EPA and DHA from transgenic Camelina sativa compared to fish oil, and the incorporation of these PUFA into blood lipids after dietary supplementation. The findings showed that postprandial EPA and DHA incorporation into blood lipids and accumulation in plasma lipids after dietary supplementation was as good as that achieved with fish oil. The oil derived from this transgenic plant was well tolerated. This review also discusses the implications for human nutrition, marine ecology and agriculture.

Characterising the nutritional status of children with primary ciliary dyskinesia.

INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare, heterogeneous genetic disorder where impaired mucociliary clearance is caused by dysfunctional motile cilia leading to bronchiectasis. There is limited evidence characterising the nutritional status of children with PCD, although lower body mass index (BMI) z-score has been associated with worse lung function (FEV1). METHODS: All children (n = 43) with PCD, aged <16 years, from a single tertiary centre were prospectively enrolled. Information on clinical phenotype and nutritional status including bioelectrical impedance spectroscopy (BIS) phase-angle was collected. RESULTS: There was a weak positive association between height-for-age z-score (HAZ) and FEV1 z-score (n = 28, r = 0.4, p = 0.049). Those with a low fat free mass index (<-2 z scores) had a lower BMI z score (-1.3 ± 1.2 vs. 0.8 ± 0.7, p = 0.0002). BIS phase angle identified more patients at nutritional risk than using moderate malnutrition cut-offs of either HAZ or BMI ≤ -2 z scores alone (21% vs. 4.6% vs. 6.9% respectively). PCD patients had a higher incidence of vitamin D insufficiency (<50 nmoL/L) (54%) and deficiency (<30 nmoL/L) (26%) than healthy children. CONCLUSIONS: We have characterised the nutritional phenotype of a cohort of children with PCD. Monitoring vitamin D levels is important in PCD patients. There is a weak association between lung function and nutritional status, and measures of BIS phase-angle. The use of BIS phase-angle may allow for early identification of at risk children and may therefore be of benefit for nutritional assessments in the clinical setting. These findings will help inform a future nutritional intervention strategy in children with PCD.

Maternal diet and its influence on the development of allergic disease.

The early presentation of childhood allergies and the rise in their prevalence suggest that changes in early-life exposures may increase the predisposition. Very early-life exposures may act upon the developing foetal immune system and include infection, environmental tobacco smoke, other pollutants and nutrients provided via the mother. Three nutrients have come under close scrutiny: vitamin D, omega 3 polyunsaturated fatty acids (PUFAs) and folate (or the synthetic form, folic acid). Much of the data on these nutrients are observational although some randomised, placebo-controlled trials have been conducted with omega 3 PUFAs and one with vitamin D. Some studies with omega 3 PUFA supplements in pregnancy have demonstrated immunomodulatory effects on the neonate and a reduction in risk of early sensitisation to allergens. A few studies with omega 3 polyunsaturated fatty acid supplements in pregnancy have shown a reduction in proportion of children affected by allergic symptoms (food allergy) or in symptom severity (atopic dermatitis). Observational studies investigating the association of maternal vitamin D intake or maternal or neonatal vitamin D status have been inconsistent. One randomised, controlled trial of vitamin D supplementation during pregnancy did not show any significant effect on allergic outcome in the offspring. Studies investigating the association between maternal folic acid or folate intake or maternal or neonatal folate status and offspring risk of allergic disease have been equivocal. Further evidence is required to clarify whether increased intake of these nutrients during pregnancy influences allergic disease in the offspring. In the light of current evidence, mothers should not either increase or avoid consuming these nutrients to prevent or ameliorate allergic disease in their offspring. However, these essential nutrients each have important roles in foetal development. This is reflected in current government recommendations for intake of these nutrients by pregnant women.

Fish oil supplementation decreases oxidative stress but does not affect platelet-activating factor bioactivity in lungs of asthmatic rats.

Dietary fish oil supplementation increases the content of n-3 polyunsaturated fatty acids (PUFA) in cellular membranes. The highly unsaturated nature of n-3 PUFA could result in an enhanced lipid peroxidation in the oxidative environment characteristic of asthma. The oxidative reaction cascade culminates in an increased production of components associated to oxidative stress and of an important proinflammatory mediator platelet-activating factor (PAF)-like lipid. We evaluated the effect of fish oil supplementation in asthmatic rats upon the PAF bioactivity and parameters related to oxidative stress in the lung. Fish oil supplementation of asthmatic rats resulted in lower concentrations of nitrite (1.719 ± 0.137 vs. 2.454 ± 0.163 nmol/mL) and lipid hydroperoxide (72.190 ± 7.327 vs. 120.200 ± 11.270 nmol/mg protein). In asthmatic animals, fish oil increased the activities of superoxide dismutase (EC 1.15.1.1) (33.910 ± 2.325 vs. 24.110 ± 0.618 U/mg protein) and glutathione peroxidase (EC 1.11.1.9) (164.100 ± 31.250 vs. 12.590 ± 5.234 U/mg protein). However, fish oil did not affect PAF bioactivity in lung tissue of asthmatic rats (0.545 ± 0.098 340/380 vs. 0.669 ± 0.101 340/380 nm ratio). Considering the two-step process--oxidative stress and PAF bioactivity--fish oil exhibited a divergent action on these aspects of asthmatic inflammation, since the supplement lowered oxidative stress in the lungs of asthmatic rats, presenting an antioxidant effect, but did not affect PAF bioactivity. This suggests a dual effect of fish oil on oxidative stress and inflammation in asthma.

Pre-trial quality assurance processes for an intensity-modulated radiation therapy (IMRT) trial: PARSPORT, a UK multicentre Phase III trial comparing conventional radiotherapy and parotid-sparing IMRT for locally advanced head and neck cancer.

The purpose of this study was to compare conventional radiotherapy with parotid gland-sparing intensity-modulated radiation therapy (IMRT) using the PARSPORT trial. The validity of such a trial depends on the radiotherapy planning and delivery meeting a defined standard across all centres. At the outset, many of the centres had little or no experience of delivering IMRT; therefore, quality assurance processes were devised to ensure consistency and standardisation of all processes for comparison within the trial. The pre-trial quality assurance (QA) programme and results are described. Each centre undertook exercises in target volume definition and treatment planning, completed a resource questionnaire and produced a process document. Additionally, the QA team visited each participating centre. Each exercise had to be accepted before patients could be recruited into the trial. 10 centres successfully completed the quality assurance exercises. A range of treatment planning systems, linear accelerators and delivery methods were used for the planning exercises, and all the plans created reached the standard required for participation in this multicentre trial. All 10 participating centres achieved implementation of a comprehensive and robust IMRT programme for treatment of head and neck cancer.

Fatty acid composition abnormalities in atopic disease: evidence explored and role in the disease process examined.

Summary There is a hypothesis causally linking excess intake of n-6 polyunsaturated fatty acids (PUFAs) to atopic disease. Under most dietary conditions, the main precursor of eicosanoids is the n-6 PUFA arachidonic acid (AA). AA-derived eicosanoids play many roles in sensitization to allergens and in allergic inflammation. Long chain n-3 PUFAs inhibit AA incorporation into cell membranes and inhibit AA metabolism to eicosanoids. It is hypothesized that atopy is associated with a higher n-6 PUFA status and with a low n-3 PUFA status. However, measurements of fatty acid composition do not provide a clear picture that such fatty acid abnormalities exist in atopy with no really clear pattern of altered status of a particular fatty acid or a particular fatty acid family. There are few reports of elevated linoleic acid in atopy. Some studies report lower amounts of the n-6 PUFAs, including AA, and of long chain n-3 PUFAs in atopy, although observations on this are not consistent. Taken together these data clearly do not support the hypothesis that atopy is somehow associated with a high exposure to, and status of, n-6 PUFAs. Intervention studies with n-3 PUFAs in pregnant women, infants and children suggest some clinical benefits, although how long lasting these are remains to be determined. The observation that there may be low AA status in atopy suggests that fish oil intervention, which targets AA status and metabolism, may not be ideal and that a combination of fish oil with some longer chain n-6 PUFAs may be more efficacious.

What is the optimum breast plan: a study based on the START trial plans.

Each year thousands of women within the UK are treated with radiotherapy for breast cancer. The majority of these women are treated using a medial and lateral tangential field. This study evaluates the plans submitted to the quality assurance (QA) team of the START trial and investigates some of the differences between departments. Throughout the START trial, hardcopies of the radiotherapy dose distribution on the central slice for one in three women were submitted to the QA team for analysis. The QA team measured physical parameters including breast size and lung depth as well as noting parameters used for the radiotherapy delivery including beam energy, field size and wedge angle. Over 1400 plans from 36 centres were analysed. The mean patient separation was 19.7 cm (SD 2.7 cm) with a mean lung depth of 1.5 cm (SD 0.7 cm). The modal beam energy was 6 MV and the mean wedge angle was 23 degrees . Significant differences in the choice of wedge angle between departments were noted; however, in 90% of cases the resultant plan complied with the maximum dose gradient of 10% on the central axis specified by the trial protocol. Less than 3% (37 plans) had dose gradients of greater than 12%. This resulted in a mean dose gradient for all patients on the central axis of 5.7% (SD 2.9%).

Verification films: a study of the daily and weekly reproducibility of breast patient set-up in the START trial.

AIMS: Verification of patient position in radiotherapy by the use of portal images is a current practice in most radiotherapy departments. All patients within the Standardisation of Breast Radiotherapy Trial (START) were required to have on-treatment verification images. Measurements of maximum lung and breast depth from these were used to provide details for the case-report forms. This study was undertaken to validate these measurements, assess the reproducibility of patients' set-up within the START trial and to compare reproducibility on a day-to-day basis with reproducibility over a longer period. Analysis also included a subjective assessment of image quality. MATERIALS AND METHODS: Fifty-three patients from 29 departments were studied. Some centres used electronic portal imaging and others used film. Where film verification was the method of choice, information was collected about the type of film and cassette used. RESULTS: The correlation coefficients for inter- and intra-observer variability of breast and lung depth were 0.99. Comparing maximum breast depth on weekly and daily images, the median per cent standard deviation of breast depth was 4% and 3%, respectively. The mean standard deviation of breast depth for all patients, which gives an indication of the individual patient variability, was 5.5 +/- 2.2 mm for weekly and 3.9 +/- 1.5 mm for daily measurements. For lung depth, mean standard deviation was 6.8 +/- 2.5 mm for weekly and 6.8 +/- 2.8 mm for daily measurements. Images taken using Kodak X-omat V film were inferior to those taken with films in corresponding cassettes. CONCLUSION: Differences between lung depth measured in simulator and on the treatment unit were evident for many patients. There was little difference in the standard deviations of breast and lung depth for daily and weekly verification films on the treatment machine.

Effect of Cleome arabica leaf extract, rutin and quercetin on soybean lipoxygenase activity and on generation of inflammatory eicosanoids by human neutrophils.

The effects of Cleome arabica leaf extract, rutin and quercetin on soybean lipoxygenase (Lox) activity and on calcium ionophore (A23187)-stimulated generation of the leukotriene B4 and prostaglandin E2 by human neutrophils were examined. The extract (25 microg/ml), rutin (25 microM) and quercetin (25 microM) inhibited LTB4 synthesis at all concentrations of A23187 used. The extract at 1-100 microg/ml and rutin at 1-100 microM inhibited LTB4 generation by neutrophils stimulated with 1 microM A23187 by about 50%. PGE2 production in response to different concentrations of A23187 was affected in a biphasic manner by the extract and rutin. Quercetin at 1-100 microM caused concentration-dependent inhibition of LTB4 and PGE2 production. The extract, rutin and quercetin caused concentration-dependent inhibition of soybean Lox activity. These results indicate that rutin, quercetin and an extract of C. arabica containing these compounds inhibit Lox activity, consequently decreasing LTB4 production. Thus, these compounds or extracts containing them may be beneficial for the treatment of inflammatory conditions, particularly those characterised by excessive leukotriene generation.

Irradiation of the heart during tangential breast treatment: a study within the START trial.

Radiotherapy to the breast is often given as a component of the treatment for women with breast cancer. It has been shown to increase overall survival although an increase in cardiac mortality has also been noted. This study was undertaken as part of the START trial quality assurance programme to record and evaluate the cardiac dose using modern radiotherapy techniques. Departments randomizing patients into the START trial and who had CT facilities for planning breast patients were invited to take part. 62 patients were included. CT slices were taken at the level of the maximum heart depth and on the treatment field central axis. Each patient was planned in the normal way and the distributions were analysed by the quality assurance team at Mount Vernon Hospital. The maximum heart position was found to be inferior to the central axis used for breast planning for the majority of patients; mean position 2.3 cm inferior with a mean maximum heart depth of 0.55 cm. For 45% of patients the maximum heart dose was less than 50% of the prescribed dose. The study showed that the volume of irradiated cardiac tissue has decreased compared with earlier studies, and also highlighted the need to scan away from the central axis if the dose to cardiac tissue is to be assessed.

In vitro effects of eicosanoids derived from different 20-carbon fatty acids on T helper type 1 and T helper type 2 cytokine production in human whole-blood cultures.

BACKGROUND: Different series prostaglandins (PGs) and leukotrienes (LTs) are synthesized from different 20 carbon fatty acid precursors. The effects of the different series of PGs and LTs on production of T helper type 1 (Th1) and Th2 cytokines by human cells are not well established. OBJECTIVE: To characterize the influence of PGs and LTs produced from different fatty acid precursors on the Th1 and Th2 cytokine profile in mitogen-stimulated human whole-blood cultures. METHODS: Blood from healthy adult males was diluted and cultured with concanavalin A in the presence or absence of a range of concentrations of various PGs or LTs. Cytokine concentrations in culture supernatants were analysed by enzyme-linked immunosorbent assay (ELISA). RESULTS: PGE1, PGE2 and PGE3 significantly and dose-dependently decreased the concentrations of the Th1 cytokines IL-2 and IFN-gamma by up to 50% and 70%, respectively. The three PGs exhibited similar potency towards IFN-gamma production. At the highest concentration used (10-6 m) PGE1, but not PGE2 or PGE3, increased the concentration of the Th2 cytokine IL-4 by about 70%. IL-10 production was not affected by PGs. The ratio of the concentrations of IFN-gamma to IL-4 was significantly decreased at PGE concentrations of 10-7 and 10-6 M with all three PGEs having similar effects. LTB4, LTC4 and LTC5 did not significantly affect production of the cytokines studied. CONCLUSION: PGE produced from different fatty acids significantly decrease Th1 cytokine production resulting in a shift in the Th1, Th2 balance in favour of a Th2 response. PGE produced from different fatty acid precursors are equipotent in their effects on human T lymphocytes. Thus, although changes in the pattern of dietary fatty intakes may contribute to the increased prevalence of atopic disease, this would probably not be mediated through substitution of one PGE with another from a different series. It may, however, be mediated through a change in the total amount of PGE produced at the site of antigen presentation.

Implementation of IMRT in the radiotherapy department.

This paper describes the implementation of intensity modulated radiotherapy (IMRT) in a radiotherapy department. When preparing to set-up an IMRT programme, it is important to review departmental protocols with regard to immobilization, CT planning, treatment planning and verification. Any additional quality assurance steps also need to be fully understood. A new IMRT programme is most likely to be successful if it builds on established clinical experience with three-dimensional conformal radiotherapy (CRT). Training of radiographers, clinicians and physicists is critical, and both team-work and communication are vital to ensure a smooth transition from 3DCRT to IMRT delivery in the clinic.

Fatty acids and lymphocyte functions.

The immune system acts to protect the host against pathogenic invaders. However, components of the immune system can become dysregulated such that their activities are directed against host tissues, so causing damage. Lymphocytes are involved in both the beneficial and detrimental effects of the immune system. Both the level of fat and the types of fatty acid present in the diet can affect lymphocyte functions. The fatty acid composition of lymphocytes, and other immune cells, is altered according to the fatty acid composition of the diet and this alters the capacity of those cells to produce eicosanoids, such as prostaglandin E2, which are involved in immunoregulation. A high fat diet can impair lymphocyte function. Cell culture and animal feeding studies indicate that oleic, linoleic, conjugated linoleic, gamma-linolenic, dihomo-gamma-linolenic, arachidonic, alpha-linolenic, eicosapentaenoic and docosahexaenoic acids can all influence lymphocyte proliferation, the production of cytokines by lymphocytes, and natural killer cell activity. High intakes of some of these fatty acids are necessary to induce these effects. Among these fatty acids the long chain n-3 fatty acids, especially eicosapentaenoic acid, appear to be the most potent when included in the human diet. Although not all studies agree, it appears that fish oil, which contains eicosapentaenoic acid, down regulates the T-helper 1-type response which is associated with chronic inflammatory disease. There is evidence for beneficial effects of fish oil in such diseases; this evidence is strongest for rheumatoid arthritis. Since n-3 fatty acids also antagonise the production of inflammatory eicosanoid mediators from arachidonic acid, there is potential for benefit in asthma and related diseases. Recent evidence indicates that fish oil may be of benefit in some asthmatics but not others.

In vitro effects of eicosanoids derived from different 20-carbon Fatty acids on production of monocyte-derived cytokines in human whole blood cultures.

INTRODUCTION: Prostaglandins (PG) and leukotrienes (LT) are usually formed from arachidonic acid (e.g. PGE(2), LTB(4), LTC(4)). The anti-inflammatory effects of fish oil may be mediated through the production of alternative PG and/or LT formed from eicosapentaenoic acid (e.g. PGE(3), LTC(5)). This study examines the effects of PG and LT derived from different fatty acid precursors on lipopolysaccharide-induced cytokine production by cultured human whole blood. Methods Human whole blood was diluted 1:5 and incubated for 48h with lipopolysaccharide. PGE and LT were added and the concentrations of inflammatory cytokines in the cell culture supernatants determined. RESULTS: Tumour necrosis factor (TNF)-alpha concentrations were significantly decreased by the addition of PGE. At the maximum concentration used (10(-6)M) TNF-alpha concentration was reduced to 100%, 90% and 70% by PGE(1), PGE(2) and PGE(3) respectively. Likewise, interleukin (IL)-1beta concentration was decreased to 60%, 30% and 40% by 10(-6)M PGE(1), PGE(2) and PGE(3), respectively. IL-6 and IL-10 concentrations were not altered by PG. LTB(4), LTC(4) or LTC(5) did not significantly affect cytokine concentrations. CONCLUSIONS: PGE inhibit lipopolysaccharide-stimulated TNF-alpha and IL-1beta production in human whole blood cultures. PGE(1), PGE(2) and PGE(3) show a similar pattern and magnitude of effect. This suggests that the anti-inflammatory effects of dietary fish oil may not be mediated through a simple substitution of one family of eicosanoids for another.

Dietary fatty acids influence the production of Th1- but not Th2-type cytokines.

C57B16 mice were fed for 6 weeks on a low-fat diet or on high-fat diets containing coconut oil (rich in saturated fatty acids), safflower oil [rich in n-6 polyunsaturated fatty acids (PUFAs)], or fish oil (rich in n-3 PUFAs) as the main fat sources. The fatty acid composition of the spleen lymphocytes was influenced by that of the diet fed. Thymidine incorporation into concanavalin A-stimulated spleen lymphocytes and interleukin (IL)-2 production were highest after feeding the coconut oil diet. Interferon (IFN)-gamma production was decreased by safflower oil or fish oil feeding. IL-4 production was not significantly affected by diet, although production was lowest by lymphocytes from fish oil-fed mice. The ratio of production of Th1- to Th2-type cytokines (determined as the IFN-gamma/IL-4 ratio) was lower for lymphocytes from mice fed the safflower oil or fish oil diets. After 4 h of culture, IL-2 mRNA levels were higher in cells from mice fed coconut oil, and IFN-gamma mRNA levels were higher in cells from mice fed coconut oil or safflower oil. After 8 h of culture, IL-2, IFN-gamma, and IL-4 mRNA levels were lowest in cells from mice fed fish oil. The ratio of the relative levels of IFN-gamma mRNA to IL-4 mRNA was highest in cells from mice fed coconut oil and was lowest in cells of mice fed fish oil. The influence of individual fatty acids on IL-2 production by murine spleen lymphocytes was examined in vitro. Although all fatty acids decreased IL-2 production in a concentration-dependent manner, saturated fatty acids were the least potent and n-3 PUFAs the most potent inhibitors, with n-6 PUFAs falling in between in terms of potency. It is concluded that saturated fatty acids have minimal effects on cytokine production. In contrast, PUFAs act to inhibit production of Th1-type cytokines with little effect on Th2-type cytokines; n-3 PUFAs are particularly potent. The effects of fatty acids on cytokine production appear to be exerted at the level of gene expression.

An olive oil-rich diet reduces scavenger receptor mRNA in murine macrophages.

During atherogenesis, a pathological accumulation of lipids occurs within aortic intimal macrophages through uptake of oxidised LDL via scavenger receptors. Here we investigated whether some of the anti-atherosclerotic effects ascribed to an olive oil rich-diet are mediated through effects on macrophage scavenger receptors (MSR). Male C57 Bl6 mice aged 6 weeks were fed for 12 weeks on a low-fat diet (containing 25 g corn oil/kg) or on high-fat diets containing 200 g coconut oil, olive oil or safflower oil/kg. Thioglycollate-elicited peritoneal macrophages were analysed for fatty acid composition by GC and the levels of mRNA coding for three MSR (MSRA type I, MSRA type II and CD36) were measured by reverse-transcription polymerase chain reaction. Feeding mice diets enriched with different fats resulted in significant differences in the fatty acid profile of macrophages, which reflected the fatty acid compositions of the diets. These differences were accompanied by a lower level of mRNA for MSRA type I, MSRA type II and CD36 in macrophages from mice fed an olive-oil-enriched diet compared with the mice fed on the low-fat diet. These data suggest that part of the protective effect of olive oil against atherosclerosis might be via reducing macrophage uptake of oxidised LDL. Whether this effect is due to the downregulation of gene transcription directly by unsaturated fatty acids or is the result of the effect of monounsaturated fatty acids or other components of olive oil on LDL composition and oxidation remains to be ascertained.

Influence of age and dietary fish oil on plasma soluble adhesion molecule concentrations.

Soluble forms of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin (termed sICAM-1, sVCAM-1 and sE-selectin respectively) are found in the plasma, and are elevated during inflammatory conditions in which there is increased expression of the cellular forms of the molecules on endothelial and other cells. sICAM-1, sVCAM-1 and sE-selectin concentrations were measured in the plasma of 140 healthy Caucasian subjects aged between 18 and 75 years (100 males/40 females). sICAM-1 concentrations varied between 59.9 and 299.7 ng/ml (median 150 ng/ml), sVCAM-1 concentrations varied between 222.8 and 1672.9 ng/ml (median 662 ng/ml) and sE-selectin concentrations varied between 12.4 and 90.3 ng/ml (median 45.5 ng/ml). There were significant positive linear correlations between age and the plasma concentrations of sICAM-1 (r=0.580; P<0.001) and sVCAM-1 (r=0.392; P<0.001), which were retained when the effects of gender, body mass index and fasting plasma triacylglycerol and total cholesterol concentrations were controlled for. The significant positive linear correlation between age and the plasma concentration of sE-selectin (r=0.234; P=0.027) was lost when other variables were controlled for. Male subjects <40 years of age had significantly lower plasma concentrations of both sICAM-1 and sVCAM-1 than males >55 years of age (both P<0.001), but the difference in plasma sE-selectin concentrations between the age groups did not reach significance (P=0.073). Subgroups of 16 males aged <40 years and 12 elderly subjects (>55 years of age) participated in a doubled-blind, placebo-controlled study of fish oil supplementation over 12 weeks. The level of eicosapentaenoic acid in plasma phospholipids did not change with placebo supplementation, but was significantly increased with fish oil supplementation in both young male and elderly subjects (median increase 200%). sICAM-1, sVCAM-1 and sE-selectin concentrations were unaffected by supplementation with placebo in either young male or elderly subjects. sICAM-1 concentrations were unaffected by fish oil supplementation. sE-selectin concentrations were significantly increased by fish oil supplementation in young males (P=0.043; median increase 38%), but fish oil tended to decrease plasma sE-selectin concentrations in the elderly subjects (P=0.075), with a median decrease of 11%. sVCAM-1 concentrations were unaffected by fish oil supplementation in young males. Fish oil supplementation significantly decreased plasma sVCAM-1 concentrations in the elderly subjects (P=0.043), with a median decrease of 20% (range 16-60%). These observations suggest that fish oil decreases endothelial activation in elderly subjects.

Influence of dietary supplementation with long-chain n-3 or n-6 polyunsaturated fatty acids on blood inflammatory cell populations and functions and on plasma soluble adhesion molecules in healthy adults.

Greatly increasing the amounts of flaxseed oil [rich in alpha-linolenic acid (ALNA)] or fish oil (FO); [rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] in the diet can decrease inflammatory cell functions and so might impair host defense. The objective of this study was to determine the effect of dietary supplementation with moderate levels of ALNA, gamma-linolenic acid (GLA), arachidonic acid (ARA), DHA, or FO on inflammatory cell numbers and functions and on circulating levels of soluble adhesion molecules. Healthy subjects aged 55 to 75 yr consumed nine capsules per day for 12 wk. The capsules contained placebo oil (an 80:20 mix of palm and sunflowerseed oils) or blends of placebo oil with oils rich in ALNA, GLA, ARA, or DHA or FO. Subjects in these groups consumed 2 g ALNA; approximately 700 mg GLA, ARA, or DHA; or 1 g EPA plus DHA (720 mg EPA + 280 mg DHA) daily from the capsules. Total fat intake from the capsules was 4 g per day. None of the treatments affected inflammatory cell numbers in the bloodstream; neutrophil and monocyte phagocytosis or respiratory burst in response to E. coli; production of tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 in response to bacterial lipopolysaccharide; or plasma concentrations of soluble intercellular adhesion molecule-1. In contrast, the ALNA and FO treatments decreased the plasma concentrations of soluble vascular cell adhesion molecule-1 (16 and 28% decrease, respectively) and soluble E-selectin (23 and 17% decrease, respectively). It is concluded that, in contrast to previous reports using higher amounts of these fatty acids, a moderate increase in consumption of long-chain n-6 or n-3 polyunsaturated fatty acids does not significantly affect inflammatory cell numbers or neutrophil and monocyte responses in humans and so would not be expected to cause immune impairment. Furthermore, we conclude that moderate levels of ALNA and FO, which could be incorporated into the diet, can decrease some markers of endothelial activation and that this mechanism of action may contribute to the reported health benefits of n-3 fatty acids.