1,721,276 research outputs found
The inhibition of T-lymphocyte proliferation by fatty acids is via an eicosanoid-independent mechanism
No full textEicosanoids, in particular prostaglandin E2 (PGE2), are potent inhibitors of a number of immune responses, including lymphocyte proliferation. We have previously shown that fatty acids, especially polyunsaturated fatty acids (PUFA), inhibit mitogen-stimulated proliferation of lymphocytes. One mechanism by which fatty acids could exert their inhibitory effect is via modulation of eicosanoid synthesis. This possibility was investigated in the present study. PGE2 concentrations in the medium taken from lymphocytes cultured in the presence of a range of different fatty acids did not correlate with the inhibitory effects of the fatty acids upon lymphocyte proliferation. Although PGE2 at concentrations above 10 nM caused inhibition of lymphocyte proliferation, PGE2 at the concentration measured in lymphocyte culture medium (0.3-4 nM) was not inhibitory. PGE3 did not inhibit lymphocyte proliferation, except at high concentrations (greater than 250 nM). The maximal inhibition of proliferation caused by PGE2 or PGE3 was less than the inhibition caused by each of the fatty acids except myristic or palmitic acids. Inclusion of inhibitors of phospholipase A2, cyclo-oxygenase or lipoxygenase in the culture medium did not prevent the fatty acids from exerting their inhibitory effect on lymphocyte proliferation. The eicosanoids present in lymph node cell cultures originate from macrophages rather than lymphocytes. Depletion of macrophages from the cell preparation by adherence did not prevent fatty acids from inhibiting proliferation. Proliferation of thoracic duct lymphocytes, which are devoid of macrophages, is inhibited by fatty acids to a similar extent as proliferation of lymph node lymphocytes. These observations provide convincing evidence that the inhibition of lymphocyte proliferation by fatty acids is independent of the production of eicosanoids. Therefore, other mechanisms must be investigated if the effect of fatty acids upon lymphocyte proliferation is to be understood at a biochemical level
Long-chain n-3 fatty acids and inflammation: potential application in surgical and trauma patients
No full textLipids used in nutritional support of surgical or critically ill patients have been based on soybean oil, which is rich in the n-6 fatty acid linoleic acid (18:2n-6). Linoleic acid is the precursor of arachidonic acid (20:4n-6). In turn, arachidonic acid in cell membrane phospholipids is the substrate for the synthesis of a range of biologically active compounds (eicosanoids) including prostaglandins, thromboxanes, and leukotrienes. These compounds can act as mediators in their own right and can also act as regulators of other processes, such as platelet aggregation, blood clotting, smooth muscle contraction, leukocyte chemotaxis, inflammatory cytokine production, and immune function. There is a view that an excess of n-6 fatty acids should be avoided since this could contribute to a state where physiological processes become dysregulated. One alternative is the use of fish oil. The rationale of this latter approach is that fish oil contains long chain n-3 fatty acids, such as eicosapentaenoic acid. When fish oil is provided, eicosapentaenoic acid is incorporated into cell membrane phospholipids, partly at the expense of arachidonic acid. Thus, there is less arachidonic acid available for eicosanoid synthesis. Hence, fish oil decreases production of prostaglandins like PGE2 and of leukotrienes like LTB4. Thus, n-3 fatty acids can potentially reduce platelet aggregation, blood clotting, smooth muscle contraction, and leukocyte chemotaxis, and can modulate inflammatory cytokine production and immune function. These effects have been demonstrated in cell culture, animal feeding and healthy volunteer studies. Fish oil decreases the host metabolic response and improves survival to endotoxin in laboratory animals. Recently clinical studies performed in various patient groups have indicated benefit from this approach.<br/
Rationale for using new lipid emulsions in parenteral nutrition and a review of the trials performed in adults
No full textLipids traditionally used in parenteral nutrition are based on n-6 fatty acid-rich vegetable oils such as soyabean oil. This practice may not be optimal because it may present an excessive supply of linoleic acid. Alternatives to the use of soyabean oil include its partial replacement by so-called medium-chain TAG (MCT), olive oil or fish oil, either alone or in combination. Lipid emulsions containing MCT are well established, but those containing olive oil and fish oil, although commercially available, are still undergoing trials in different patient groups. Emulsions containing olive oil or fish oil are well tolerated and without adverse effects in a wide range of adult patients. An olive oil–soyabean oil emulsion has been used in quite small studies in critically-ill patients and in patients with trauma or burns with little real evidence of advantage over soyabean oil or MCT–soyabean oil. Fish oil-containing lipid emulsions have been used in adult patients post surgery (mainly gastrointestinal). This approach has been associated with alterations in patterns of inflammatory mediators and in immune function and, in some studies, a reduction in the length of stay in the intensive care unit and in hospital. One study indicates that peri-operative administration of fish oil may be superior to post-operative administration. Fish oil has been used in critically-ill adults. Here, the influence on inflammatory processes, immune function and clinical end points is not clear, since there are too few studies and those that are available report contradictory findings. One important factor is the dose of fish oil required to influence clinical outcomes. Further studies that are properly designed and adequately powered are required in order to strengthen the evidence base relating to the use of lipid emulsions that include olive oil and fish oil in critically-ill patients and in patients post surger
A matter of fat
No full textAcute respiratory disease syndrome (ARDS) is a common complication of critical illness, associated with significant morbidity, prolonged intensive care unit (ICU) and hospital stay, and increased mortality. Inflammation plays a central role in ARDS, with inflammatory eicosanoid mediators produced from the ?-6 fatty acid arachidonic acid, such as leukotriene B4, being involved. The ?-3 fatty acids found in fish oil exert anti-inflammatory effects, including decreasing production of inflammatory eicosanoids from arachidonic acid. The ?-3 fatty acids are effective in models relevant to ARDS. Several randomized controlled trials of enteral formulas rich in ?-3 fatty acids, often in combination with other bioactive substances, have been conducted in patients with ARDS. Four of these trials reported marked clinical benefits, 2 reported no effect, and 1 reported a negative impact. A systematic review and meta-analysis of these 7 trials identified no overall effect on ventilator-free days or on ICU-free days. There was a small reduction in ICU length of stay and no overall effect on mortality. However, the authors formally identified that trials that used high fat in both treatment and control groups showed a significant reduction in mortality, while trials that used a high, or higher, fat treatment and a low-fat control group showed a trend toward an increase in mortality. It is concluded that differences in outcome reported among these studies largely relate to the relative fat contents of the treatment and control formulas. Further, it is concluded that high-fat enteral formulas should not be used in this patient grou
Long-chain n-3 fatty acids and cardiovascular disease: further evidence and insights
No full textThe traditional Inuit diet was rich in long-chain n-3 polyunsaturated fatty acids (PUFAs), and this is believed to account for the low incidence of cardiovascular disease in Inuit populations. Epidemiological studies in Europe and North America demonstrate inverse relationships between consumption or status of long-chain n-3 PUFAs and cardiovascular morbidity and mortality. Long-chain n-3 PUFAs might act through modification of recognized risk factors such as hypertriacylglycerolemia and hypertension. Secondary prevention studies in post-myocardial infarction patients demonstrate that long-chain n-3 PUFAs, provided in the form of fish oil, reduce cardiovascular events and mortality, with an especially potent effect on sudden death. The anti-thrombotic and anti-arrhythmic actions of long-chain n-3 PUFAs may explain these effects. In addition, long-chain n-3 PUFAs are anti-inflammatory and so may act to increase atherosclerotic plaque stability. This may explain the observed reduction in cardiovascular events and mortality. A recent study has investigated this possibility. Patients awaiting carotid endarterectomy consumed control, sunflower oil, or fish oil capsules until surgery, when the atherosclerotic plaque was removed. The proportions of long-chain n-3 PUFAs were higher in carotid plaque lipids in patients receiving fish oil. Plaques from patients in the fish oil group were more likely to have thick fibrous caps and fewer signs of inflammation and to contain fewer macrophages. This may be indicative of increased plaque stability
Immunonutrition: May have beneficial effects in surgical patients
No full textThe potential to modulate the activity of the immune system by interventions with specific nutrients is termed immunonutrition. This concept may be applied to any situation in which an altered supply of nutrients is used to modify inflammatory or immune responses. However, immunonutrition has become associated most closely with attempts to improve the clinical course of critically ill and surgical patients, who will often require an exogenous supply of nutrients through the parenteral or enteral routes. Major surgery is followed by a period of immunosuppression that increases the risk of morbidity and mortality due to infection. Improving immune function during this period may reduce complications due to infection. Critically ill patients are at greater risk of adverse outcomes than surgical patients. In these patients complex variable immune and inflammatory changes occur that are only now being well defined. A biphasic response with an early hyperinflammatory response followed by an excessive compensatory response associated with immunosuppression is seen in many such patients. Here, early treatment is aimed at decreasing the inflammatory response rather than enhancing it, to abrogate the hyperinflammation and prevent the compensatory immunosuppression
The use of n-3 polyunsaturated fatty acids as therapeutic agents for inflammatory diseases
No full textWith regard to inflammatory processes, the main fatty acids of interest are the n-6 polyunsaturated fatty acid (PUFA) arachidonic acid, which is the precursor of inflammatory eicosanoids like prostaglandin E2 and leukotriene B4, and the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA and DHA are found in oily fish and fish oils. EPA and DHA inhibit arachidonic acid metabolism to inflammatory eicosanoids. They also give rise to mediators that are less inflammatory than those produced from arachidonic acid or that are anti-inflammatory. In addition to modifying the lipid mediator profile, n-3 PUFAs exert effects on other aspects of inflammation like leukocyte chemotaxis, expression of adhesion molecules and production of inflammatory cytokines. Because of their potential as anti-inflammatory agents they may be of therapeutic use in a variety of acute and chronic inflammatory settings. Evidence of their clinical efficacy is reasonably strong in some settings (e.g. in rheumatoid arthritis) but is weak in others (e.g. in inflammatory bowel diseases and asthma). More, better designed and larger trials are required in inflammatory diseases to assess the therapeutic potential of long chain n-3 PUFAs in these condition
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