58 research outputs found
Nutrient gene interactions and the inflammatory response
No full textThe function of inflammation is to combat pathogens following injury and surgery. During the inflammatory response, muscle and adipose tissue are catabolised to provide amino acids, glucose and fatty acids, for the immune response. The liver increases acute phase protein synthesis and anti-oxidant defences are enhanced by increased glutathione synthesis. Oxidants production creates a hostile environment for pathogens. The strength of the response is modulated by pro-inflammatory and anti-inflammatory cytokines. Interleukins (IL) 1 and 6 and tumour necrosis factor-? (TNF-?), fall into the first category, and IL-10 into the second. Neuroendocrine responses occur, and heat shock proteins are produced to curtail the inflammatory response. Inflammation exerts damaging and lethal effects. High production of IL-1 and TNF-? increases mortality in cerebral malaria, meningitis and sepsis. The ratio of pro- to anti-inflammatory cytokines also result in an adverse outcome to infection. High IL-6 to IL-10, and IL-10 to TNF ratios are associated with raised mortality. IL-1, IL-6 and TNF-? also play a damaging role in inflammatory disease and atheromatous plaque development. Genotype is a key factor which influences cytokine production and the strength of the inflammatory response. TNF-?, IL-1?, IL-6 and IL-10 production is strongly influenced by single nucleotide polymorphisms (SNPs) in the promoter region of the respective genes. Cytokine gene alleles are linked to increased morbidity in a range of diseases and conditions including sepsis, diabetes mellitus and cardiovascular disease. Studies on the anti-inflammatory effect of n-3 PUFAs indicate that individual genotype may influence the efficacy of immunonutrients in controlling inflammation. To improve patient outcome a better understanding is needed, of how nutrients, such as n-3 PUFAs can be used to control the inflammatory process and how individual genotype influences the response to such immunonutrients
Symposium on ‘Evidence-based nutrition’. Nutritional modulation of immune function
No full textThe inflammatory response to injury and infection, although an essential part of immune function, carries the risk of severe tissue depletion and immunosuppression. These outcomes increase morbidity and delay recovery. Evidence is accumulating that single-nucleotide polymorphisms in the genes controlling pro-inflammatory cytokine production adversely influence the response. Immunonutrition provides a means of modulating the inflammatory response to injury and infection, and thereby improves clinical outcome. n-3 Polyunsaturated fatty acids (n-3 PUFA), glutamine, arginine, S amino acids and nucleotides are important components of immunonutrient mixes. While animal model studies suggest that all these components may exert a beneficial effect in patients, the number of large randomized placebo-controlled trials utilizing immunonutrition is fairly limited and the observed effects are relatively small. Meta-analyses suggest that while immunonutrition may not reduce mortality rates, a reduction in hospital length of stay, decreased requirements for ventilation and lower infection rates are achieved by this mode of nutrition. The present paper discusses some underlying reasons for the difficulty in demonstrating the clinical efficacy of immunonutrition. Paramount among these reasons is the antioxidant status and genetic background of the patient. A number of studies suggest that there is an inverse relationship between inflammation and T-cell function. Immuno-enhancive effects have been shown in a number of studies in which n-3 PUFA, glutamine and N-acetyl cysteine have been employed. All these nutrients may exert their effects by suppressing inflammation; n-3 PUFA by direct suppression of the process and glutamine and N-acetyl cysteine by acting indirectly on antioxidant status. Glutamine and nucleotides exert a direct effect on lymphocyte proliferation. Preliminary data suggests that not all genotypes are equally sensitive to the effects of immunonutrition. When further studies have been conducted to discern the precise interaction between each individual’s genotype of relevance to the response to injury and infection, and immunonutrients, the level of precision in the application of immunonutrition will undoubtedly improve.<br/
The effect of graded levels of dietary casein, with or without methionine supplementation, on glutathione concentration in unstressed and endotoxin-treated rats
No full textGlutathione (GSH) concentration was measured in rats fed either graded levels of dietary casein (experiment 1; 180 g, 120 g, 80 g, or 60 g protein/kg diet) or graded levels of dietary casein, supplemented with methionine to equalize dietary sulfur amino acid content to that seen in an 180 g/kg casein diet supplemented with 0.3 g L-methionine/kg diet (experiment 2; 180 g protein +0.3 g L-methionine, 80 g protein +6.70 g L-methionine, or 60 g protein +7.45 g L-methionine/kg diet). Rats were given an inflammatory challenge by intraperitoneal injection of endotoxin (lipopolysaccharide from Escherichia coli), and were compared with ad libitum and pair-fed controls. Glutathione concentration in various organs (liver, lung, spleen, and thymus) decreased in animals fed the low-protein diets (80 g or 60 g/kg diet). Addition of the sulfur amino acid, methionine, to the low-protein diets restored glutathione concentrations in animals fed ad libitum and prevented the fall in GSH concentration, which occurred in lung, spleen, and thymus in response to the endotoxin. Despite the similarity in the amount of sulfur amino acid consumed between the groups fed the 180 g protein +0.3 g L-methionine and the 60 g protein +7.45 g L-methionine/kg diet, in experiment 2, hepatic GSH concentration significantly increased in the latter group, in animals fed ad libitum and in the endotoxin-treated animals, but not in the pair-fed controls
Polyunsaturated fatty acids, inflammation and immunity
No full textConsumption of n-6 polyunsaturated fatty acids greatly exceeds that of n-3 polyunsaturated fatty acids. The n-6 polyunsaturated fatty acid arachidonic gives rise to the eicosanoid family of inflammatory mediators (prostaglandins, leukotrienes and related metabolites) and through these regulates the activities of inflammatory cells, the production of cytokines and the various balances within the immune system. Fish oil and oily fish are good sources of long chain n-3 polyunsaturated fatty acids. Consumption of these fatty acids decreases the amount of arachidonic acid in cell membranes and so available for eicosanoid production. Thus, n-3 polyunsaturated fatty acids act as arachidonic acid antagonists. Components of both natural and acquired immunity, including the production of key inflammatory cytokines, can be affected by n-3 polyunsaturated fatty acids. Although some of the effects of n-3 fatty acids may be brought about by modulation of the amount and types of eicosanoids made, it is possible that these fatty acids might elicit some of their effects by eicosanoid-independent mechanisms. Such n-3 fatty acid-induced effects may be of use as a therapy for acute and chronic inflammation, and for disorders which involve an inappropriately activated immune response.<br/
Genomic interactions with disease and nutrition
No full textThe putative influence of genomic factors on the responsiveness to nutrient intake is a newly developed field of research. As well, there is growing interest for determining the interactions between nutrient, inflammation and aging and the possible impact on lifespan and disease development.Inflammation adversely affects health in many diseases with an inflammatory basis, such as atherosclerosis, obesity and type 2 diabetes mellitus. The metabolic effects of inflammation are mediated by pro-inflammatory cytokines. Metabolic effects include insulin insensitivity, hyperlipidemia, muscle protein loss and oxidant stress. Aging is also characterized by an increase in inflammatory stress and contains some of the hallmarks of inflammatory disease. It is also a phase of life when inflammatory diseases rise in incidence.Evidence is accumulating that the individual level of cytokine production is influenced by single nucleotide polymorphisms (SNPs) in cytokine genes. The combination of SNPs might control the relative level of inflammatory stress following inflammatory stimuli and diseases. These genomic characteristics might therefore influence lifespan, morbidity and mortality in diseases with an infectious or inflammatory basis.Recent studies indicate that genotypic factors may influence the effectiveness of such immunonutrients as anti-oxidants and n-3 pollyunsaturated fatty acids.A better understanding of this aspect of nutrient gene interactions and of the genomic factors which influence the intensity of inflammation in disease will help in the targeting of nutritional therapy
Genotypic influences on metabolic alterations during inflammation and the nutritional outcome
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