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Long-chain ω-3 PUFAs such as DHA and EPA are often present in high amounts in algae and fish. DHA in particular is crucial for the proper development and functioning of the brain because it is the main structural component of ω-3 PUFA in the brain. This makes it an indispensable element of the phospholipids of the nervous membrane. The purpose of this article is to present the benefits of Omega-3 acids in the functioning of the nervous system. The text discusses a literature review focusing on the impact of omega-3 fatty acids. Polyunsaturated fatty acids (PUFAs) are essential for overall health and have been extensively studied for their contributions to human well-being and disease management. Recent research indicates their effectiveness in preventing and treating various diseases. Omega-3 PUFAs have been identified as therapeutic agents, particularly in combating inflammatory conditions like cardiovascular and neurodegenerative diseases. The aim of this article is to present the benefits of omega-3 fatty acids supplementation. Publications outlining properties of polyunsaturated fatty acids on the brain and articles presenting the effects of polyunsaturated fatty acids were reviewed using the Pubmed platform. The review included the keywords "Omega-3 fatty acids" "DHA" "EPA" "PUFA.

Background: Many nutrients have powerful immunomodulatory actions with the potential to alter susceptibility to coronavirus disease 2019 (COVID-19) infection, progression to symptoms, likelihood of severe disease, and survival., Objective: The aim was to review the latest evidence on how malnutrition across all its forms (under- and overnutrition and micronutrient status) may influence both susceptibility to, and progression of, COVID-19., Methods: We synthesized information on 13 nutrition-related components and their potential interactions with COVID-19: overweight, obesity, and diabetes; protein-energy malnutrition; anemia; vitamins A, C, D, and E; PUFAs; iron; selenium; zinc; antioxidants; and nutritional support. For each section we provide: 1) a landscape review of pertinent material; 2) a systematic search of the literature in PubMed and EMBASE databases, including a wide range of preprint servers; and 3) a screen of 6 clinical trial registries. All original research was considered, without restriction to study design, and included if it covered: 1) severe acute respiratory syndrome coronavirus (CoV) 2 (SARS-CoV-2), Middle East respiratory syndrome CoV (MERS-CoV), or SARS-CoV viruses and 2) disease susceptibility or 3) disease progression, and 4) the nutritional component of interest. Searches took place between 16 May and 11 August 2020., Results: Across the 13 searches, 2732 articles from PubMed and EMBASE, 4164 articles from the preprint servers, and 433 trials were returned. In the final narrative synthesis, we include 22 published articles, 38 preprint articles, and 79 trials., Conclusions: Currently there is limited evidence that high-dose supplements of micronutrients will either prevent severe disease or speed up recovery. However, results of clinical trials are eagerly awaited. Given the known impacts of all forms of malnutrition on the immune system, public health strategies to reduce micronutrient deficiencies and undernutrition remain of critical importance. Furthermore, there is strong evidence that prevention of obesity and type 2 diabetes will reduce the risk of serious COVID-19 outcomes. This review is registered at PROSPERO as CRD42020186194., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

The world is currently in the grips of the coronavirus disease (COVID-19) pandemic, caused by the SARS-CoV-2 virus, which has mutated to allow human-to-human spread. Infection can cause fever, dry cough, fatigue, severe pneumonia, respiratory distress syndrome and in some instances death. COVID-19 affects the immune system by producing a systemic inflammatory response, or cytokine release syndrome. Patients with COVID-19 have shown a high level of pro-inflammatory cytokines and chemokines. There are currently no effective anti-SARS-CoV-2 viral drugs or vaccines. COVID-19 disproportionately affects the elderly, both directly, and through a number of significant age-related comorbidities. Undoubtedly, nutrition is a key determinant of maintaining good health. Key dietary components such as vitamins C, D, E, zinc, selenium and the omega 3 fatty acids have well-established immunomodulatory effects, with benefits in infectious disease. Some of these nutrients have also been shown to have a potential role in the management of COVID-19. In this paper, evidence surrounding the role of these dietary components in immunity as well as their specific effect in COVID-19 patients are discussed. In addition, how supplementation of these nutrients may be used as therapeutic modalities potentially to decrease the morbidity and mortality rates of patients with COVID-19 is discussed., (Copyright © 2020 Elsevier B.V. All rights reserved.)

As the infected cases of COVID-19 reach more than 20 million with more than 778,000 deaths globally, an increase in psychiatric disorders including anxiety and depression has been reported. Scientists globally have been searching for novel therapies and vaccines to fight against COVID-19. Improving innate immunity has been suggested to block progression of COVID-19 at early stages, while omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been shown to have immunomodulation effects. Moreover, n-3 PUFAs have also been shown to improve mood disorders, thus, future research is warranted to test if n-3 PUFAs may have the potential to improve our immunity to counteract both physical and mental impact of COVID-19., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Omega-3 polyunsaturated fatty acids (PUFAs) were proposed to have potential effects against inflammation and cancer. However, results from epidemiology studies remain inconsistent. We aimed to explore the associations of plasma PUFAs with EC recurrence and all-cause mortality., Method: Women diagnosed with endometrial cancer (EC) between 2008 and 2013 and underwent surgery at Fudan University Shanghai Cancer Center of China were recruited. Survival status was followed up through September 2017. EC recurrence and total cause deaths were identified through medical record and telephone interview. In total, 202 patients with enough plasma samples at time of surgery were included. There were 195 patients who provided baseline plasma and survival information included in the current study. Plasma omega-3 PUFAs were measured by GC-FID. Cox Proportional Hazard model adjusted for potential cofounders was used to estimate HRs and 95% CIs., Results: Median follow-up time for patients was 58 months after surgery. A total of 13 recurrences and 11 all-cause deaths, of which, 2 deaths from EC, were identified. Level of plasma EPA was higher in recurrent patients than total patients (0.78% vs 0.51%, P = 0.015). Higher plasma eicosapentaenoic acid (EPA) level trended to have positive association with EC recurrence (P-trend = 0.04), although comparing to the lowest tertile, the highest tertile of EPA level was not significantly associated with increased risk of EC recurrence (HR T3vsT1  = 6.02; 95%CI = 0.7-52.06). The association between total omega-3 PUFA and EC recurrence tended to be stronger among patients with deeper myometrial invasion (OR = 3.41; 95%CI = 1.06-10.95; P-interaction = 0.04)., Conclusions: Higher plasma EPA level was significantly associated with EC recurrence. Further studies are warranted to confirm these findings., Trial Registration: ChiCTR1900025418; Retrospectively registered (26 August 2019); Chinses Clinical Trial Registry.

Advances in the understanding of how the immune system functions in response to diet have altered the way we think about feeding livestock and companion animals on both the short (weeks/months) and long-term (years) timelines; however, depth of research in each of these species varies. Work dedicated to understanding how immune function can be altered with diet has revealed additional functions of required nutrients such as vitamins D and E, omega-3 polyunsaturated fatty acids (PUFA), and minerals such as zinc, while feed additives such as phytogenics and probiotics add an additional layer of immunomodulating potential to modern diets. For certain nutrients such as vitamin D or omega-3 PUFA, inclusion above currently recommended levels may optimize immune function and reduce inflammation, while for others such as zinc, additional pharmacological supplementation above requirements may inhibit immune function. Also to consider is the potential to over-immunomodulate, where important functions such as clearance of microbial infections may be reduced when supplementation reduces the inflammatory action of the immune system. Continued work in the area of nutritional immunology will further enhance our understanding of the power of nutrition and diet to improve health in both livestock and companion animals. This review collects examples from several species to highlight the work completed to understand how nutrition can be used to alter immune function, intended or not., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Omega-3 ( n -3) polyunsaturated fatty acids (PUFAs) have been known to exert anti-inflammatory effects on various disease states. However, its effect on CD8 + T cell-mediated immunopathology upon viral infection has not been well elucidated yet. In this study, we investigated the possible implication of n -3 PUFAs in CD8 + T cell responses against an acute viral infection. Infection of FAT-1 transgenic mice that are capable of synthesizing n -3 PUFAs from n -6 PUFAs with lymphocytic choriomeningitis virus (LCMV) resulted in significant reduction of anti-viral CD8 + T cell responses. Interestingly, expansion of adoptively transferred wild-type (WT) LCMV-specific T cell receptor (TCR) transgenic CD8 + (P14) T cells into FAT-1 mice was significantly decreased. Also, activation of anti-viral CD4 + helper T cells was reduced in FAT-1 mice. Importantly, P14 cells carrying the fat-1 gene that were adoptively transferred into WT mice exhibited a substantially decreased ability to proliferate and produce cytokines against LCMV infection. Together, n -3 PUFAs attenuated anti-viral CD8 + T cell responses against an acute viral infection and thus could be used to alleviate immunopathology mediated by the viral infection.

Overstimulation of the pro-inflammatory pathways within brain areas responsible for sympathetic outflow is well evidenced as a primary contributing factor to the establishment and maintenance of neurogenic hypertension. However, the precise mechanisms and stimuli responsible for promoting a pro-inflammatory state are not fully elucidated. Recent work has unveiled novel compounds derived from omega-3 polyunsaturated fatty acids (ω-3 PUFAs), termed specialized pro-resolving mediators (SPMs), which actively regulate the resolution of inflammation. Failure or dysregulation of the resolution process has been linked to a variety of chronic inflammatory and neurodegenerative diseases. Given the pathologic role of neuroinflammation in the hypertensive state, SPMs and their associated pathways may provide a link between hypertension and the long-standing association of dietary ω-3 PUFAs with cardioprotection. Herein, we review recent progress in understanding the RAS-driven pathophysiology of neurogenic hypertension, particularly in regards to the chronic low-grade neuroinflammatory response. In addition, we examine the potential for an impaired resolution of inflammation process in the context of hypertension., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

In spite of therapeutic improvements in the treatment of different hematologic malignancies, the prognosis of acute myeloid leukemia (AML) treated solely with conventional induction and consolidation chemotherapy remains poor, especially in association with high risk chromosomal or molecular aberrations. Recent discoveries describe the complex interaction of immune effector cells, as well as the role of the bone marrow microenvironment in the development, maintenance and progression of AML. Lipids, and in particular omega-3 as well as omega-6 polyunsaturated fatty acids (PUFAs) have been shown to play a vital role as signaling molecules of immune processes in numerous benign and malignant conditions. While the majority of research in cancer has been focused on the role of lipid mediators in solid tumors, some data are showing their involvement also in hematologic malignancies. There is a considerable amount of evidence that AML cells are targetable by innate and adaptive immune mechanisms, paving the way for immune therapy approaches in AML. In this article we review the current data showing the lipid mediator and lipidome patterns in AML and their potential links to immune mechanisms.

Allergic conjunctivitis (AC) is one of the most common ocular surface diseases in the world. In AC, T helper type 2 (T h 2) immune responses play central roles in orchestrating inflammatory responses. However, the roles of lipid mediators in the onset and progression of AC remain to be fully explored. Although previous reports have shown the beneficial effects of supplementation of ω-3 fatty acids in asthma or atopic dermatitis, the underlying molecular mechanisms are poorly understood. In this study, a diet rich in ω-3 fatty acids alleviated AC symptoms in both early and late phases without affecting T h 2 immune responses, but rather by altering the lipid mediator profiles. The ω-3 fatty acids completely suppressed scratching behavior toward the eyes, an allergic reaction provoked by itch. Although total serum IgE levels and the expression levels of T h 2 cytokines and chemokines in the conjunctiva were not altered by ω-3 fatty acids, eosinophil infiltration into the conjunctiva was dramatically suppressed. The levels of ω-6-derived proinflammatory lipid mediators, including those with chemoattractant properties for eosinophils, were markedly reduced in the conjunctivae of ω-3 diet-fed mice. Dietary ω-3 fatty acids can alleviate a variety of symptoms of AC by altering the lipid mediator profile.-Hirakata, T., Lee, H.-C., Ohba, M., Saeki, K., Okuno, T., Murakami, A., Matsuda, A., Yokomizo, T. Dietary ω-3 fatty acids alter the lipid mediator profile and alleviate allergic conjunctivitis without modulating T h 2 immune responses.

The intestinal mucosa serves as a highly selective barrier that allows the absorption of nutrients and water while restricting microbiota access to tissues. This barrier is compromised in inflammatory conditions such as infectious colitis and inflammatory bowel disease (IBD). In response to mucosal injury, there is a temporal recruitment of leukocytes that crosstalk with epithelial cells to orchestrate repair. Specialized pro-resolving mediators (SPMs) play an important role in the resolution of inflammation and epithelial repair. SPMs actively promote resolution of inflammation by contributing to the clearance of neutrophils, stimulating efferocytosis, and promoting epithelial repair. SPMs have potential to serve as targeted therapeutic agents to be used in adjuvant therapy to promote resolution of inflammation and epithelial repair in chronic inflammatory diseases., (Copyright © 2018. Published by Elsevier Ltd.)

The purpose of this review is to explain the historical and clinical background for intravenous fish oil administration, to evaluate its results by using a product specific metaanalysis, and to stimulate further research in the immune-modulatory potential of fish oil. Concerning the immune-modulatory effects of fatty acids, a study revealed that ω-3 as well as ω-6 fatty acids would prolong transplant survival, and only a mixture with an ω-6:ω-3 ratio of 2.1:1 would give immune-neutral results. In 1998, the label of a newly registered fish oil emulsion also acknowledged this immune-neutral ratio in conjunction with ω-6 lipids. Also, two fish oil-supplemented fat emulsions, registered in 2004, used a similar ω-6:ω-3 ratio. Such an immune-neutral ω-6:ω-3 ratio denoted progress for most patients compared to pure ω-6 lipid emulsions. However, this immune-neutrality might on the other hand be responsible for the limited positive clinical results gained so far in critically ill and surgical patients where in most cases significance could only be shown for the pooled effect of numerous trials. Our product specific metaanalysis also did not reveal any differences, neither in infections rates nor in ICU or hospital length of stay. To evaluate the immune-modulatory effect of fish oil administered alone, new dose finding studies, reporting relevant clinical outcome parameters, are required. Precise mechanistic or physiological biomarkers for the indication of such a therapy should also be developed and validated., (Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Ageing of the global population has become a public health concern with an important socio-economic dimension. Ageing is characterized by an increase in the concentration of inflammatory markers in the bloodstream, a phenomenon that has been termed "inflammageing". The inflammatory response is beneficial as an acute, transient reaction to harmful conditions, facilitating the defense, repair, turnover and adaptation of many tissues. However, chronic and low grade inflammation is likely to be detrimental for many tissues and for normal functions. We provide an overview of low grade inflammation (LGI) and determine the potential drivers and the effects of the "inflamed" phenotype observed in the elderly. We discuss the role of gut microbiota and immune system crosstalk and the gut-brain axis. Then, we focus on major health complications associated with LGI in the elderly, including mental health and wellbeing, metabolic abnormalities and infections. Finally, we discuss the possibility of manipulating LGI in the elderly by nutritional interventions. We provide an overview of the evidence that exists in the elderly for omega-3 fatty acid, probiotic, prebiotic, antioxidant and polyphenol interventions as a means to influence LGI. We conclude that slowing, controlling or reversing LGI is likely to be an important way to prevent, or reduce the severity of, age-related functional decline and the onset of conditions affecting health and well-being; that there is evidence to support specific dietary interventions as a strategy to control LGI; and that a continued research focus on this field is warranted., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim: We previously reported a protective effect of maternal omega-3 fatty acid supplements on the development of immunoglobulin E (IgE)-associated disease in infancy. This study assessed omega-3 long-chain polyunsaturated fatty acids (LCPUFA) in maternal milk in relation to omega-3 LCPUFA supplementation and the development of allergic disease in their infants., Methods: This study randomised 95 pregnant women at risk of having an allergic infant, to daily supplements of 2.6 g omega-3 LCPUFA or a placebo of 2.7 g soya bean oil from gestational week 25 until 3 months of lactation. Breast milk samples were collected as colostrum, at one and 3 months. Milk fatty acids were related to allergic outcome in the infants at 24 months., Results: Omega-3 milk fatty acids were higher in women who received omega-3 supplements than the placebo group (p < 0.01). Higher proportions of milk eicosapentaenoic acid and docosahexaenoic acid and a lower arachidonic/eicosapentaenoic acid ratio were associated with an absence of IgE-associated disease in the infants. None of the children developed IgE-associated atopic eczema above a level of 0.83 mol% eicosapentaenoic acid in colostrum. [Correction added on 7 July 2016, after online publication: In the preceding sentence, the correct word should be "above" instead of "below" and this has been amended in this current version.] CONCLUSION: High omega-3 LCPUFA milk levels in mothers who received omega-3 LCPUFA supplements were related to fewer allergies in their children., (©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Bacterial and viral respiratory tract infections result in millions of deaths worldwide and are currently the leading cause of death from infection. Acute inflammation is an essential element of host defense against infection, but can be damaging to the host when left unchecked. Effective host defense requires multiple lipid mediators, which collectively have proinflammatory and/or proresolving effects on the lung. During pulmonary infections, phospholipid acyl chains and cholesterol can be chemically and enzymatically oxidized, as well as truncated and modified, producing complex mixtures of bioactive lipids. We review recent evidence that phospholipids and cholesterol and their derivatives regulate pulmonary innate and adaptive immunity during infection. We first highlight data that oxidized phospholipids generated in the lung during infection stimulate pattern recognition receptors, such as TLRs and scavenger receptors, thereby amplifying the pulmonary inflammatory response. Next, we discuss evidence that oxidation of endogenous pools of cholesterol during pulmonary infections produces oxysterols that also modify the function of both innate and adaptive immune cells. Last, we conclude with data that n-3 polyunsaturated fatty acids, both in the form of phospholipid acyl chains and through enzymatic processing into endogenous proresolving lipid mediators, aid in the resolution of lung inflammation through distinct mechanisms. Unraveling the complex mechanisms of induction and function of distinct classes of bioactive lipids, both native and modified, may hold promise for developing new therapeutic strategies for improving pulmonary outcomes in response to infection., (© Society for Leukocyte Biology.)

There are significant numbers of nutrient sensing G protein-coupled receptors (GPCRs) that can be found in cells of the immune system and in tissues that are involved in metabolic function, such as the pancreas or the intestinal epithelium. The family of free fatty acid receptors (FFAR1-4, GPR84), plus a few other metabolite sensing receptors (GPR109A, GPR91, GPR35) have been for this reason the focus of studies linking the effects of nutrients with immunological responses. A number of the beneficial anti-inflammatory effects credited to dietary fats such as omega-3 fatty acids are attributed to their actions on FFAR4.This might play an important protective role in the development of obesity, insulin resistance or asthma. The role of the short-chain fatty acids resulting from fermentation of fibre by the intestinal microbiota in regulating acute inflammatory responses is also discussed. Finally we assess the therapeutic potential of this family of receptors to treat pathologies where inflammation is a major factor such as type 2 diabetes, whether by the use of novel synthetic molecules or by the modulation of the individual's diet., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

The potential for regulating immune function in acute respiratory distress syndrome (ARDS) through enteral-administered anti-inflammatory lipids has generated much interest over the past 20 years. Yet recommendations remain inconclusive regarding the utilization of ω-3 fatty acids in patients with ARDS and acute lung injury (ALI). Studies are limited in number, with differing methods, small sample sizes, and conflicting results, making recommendations difficult to interpret., (© 2016 American Society for Parenteral and Enteral Nutrition.)

Phospholipase A2 enzymes have long been implicated in the promotion of inflammation by mobilizing pro-inflammatory lipid mediators, yet recent evidence suggests that they also contribute to anti-inflammatory or pro-resolving programs. Group IID-secreted phospholipase A2 (sPLA2-IID) is abundantly expressed in dendritic cells in lymphoid tissues and resolves the Th1 immune response by controlling the steady-state levels of anti-inflammatory lipids such as docosahexaenoic acid and its metabolites. Here, we show that psoriasis and contact dermatitis were exacerbated in Pla2g2d-null mice, whereas they were ameliorated in Pla2g2d-overexpressing transgenic mice, relative to littermate wild-type mice. These phenotypes were associated with concomitant alterations in the tissue levels of ω3 polyunsaturated fatty acid (PUFA) metabolites, which had the capacity to reduce the expression of pro-inflammatory and Th1/Th17-type cytokines in dendritic cells or lymph node cells. In the context of cancer, however, Pla2g2d deficiency resulted in marked attenuation of skin carcinogenesis, likely because of the augmented anti-tumor immunity. Altogether, these results underscore a general role of sPLA2-IID as an immunosuppressive sPLA2 that allows the microenvironmental lipid balance toward an anti-inflammatory state, exerting beneficial or detrimental impact depending upon distinct pathophysiological contexts in inflammation and cancer., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

Background: Living on a farm has repeatedly been shown to protect children from asthma and allergies. A major factor involved in this effect is consumption of unprocessed cow's milk obtained directly from a farm. However, this phenomenon has never been shown in a longitudinal design, and the responsible milk components are still unknown., Objectives: We sought to assess the asthma-protective effect of unprocessed cow's milk consumption in a birth cohort and to determine whether the differences in the fatty acid (FA) composition of unprocessed farm milk and industrially processed milk contributed to this effect., Methods: The Protection Against Allergy-Study in Rural Environments (PASTURE) study followed 1133 children living in rural areas in 5 European countries from birth to age 6 years. In 934 children milk consumption was assessed by using yearly questionnaires, and samples of the "usually" consumed milk and serum samples of the children were collected at age 4 years. Doctor-diagnosed asthma was parent reported at age 6 years. In a nested case-control study of 35 asthmatic and 49 nonasthmatic children, 42 FAs were quantified in milk samples., Results: The risk of asthma at 6 years of age was reduced by previous consumption of unprocessed farm milk compared with shop milk (adjusted odds ratio for consumption at 4 years, 0.26; 95% CI, 0.10-0.67). Part of the effect was explained by the higher fat content of farm milk, particularly the higher levels of ω-3 polyunsaturated FAs (adjusted odds ratio, 0.29; 95% CI, 0.11-0.81)., Conclusion: Continuous farm milk consumption in childhood protects against asthma at school age partially by means of higher intake of ω-3 polyunsaturated FAs, which are precursors of anti-inflammatory mediators., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Dysregulation of adipokines is a hallmark of obesity. Polyunsaturated fatty acids in fish oil may exert anti-inflammatory effects on adipose tissue mitigating the dysregulation of adipokines thereby preventing obesity. This study investigated the effects of high-fat diets containing different amounts of n3 polyunsaturated fatty acids (PUFA) on adiposity and adipokine production in mice. Mice were fed a low-fat or a high-fat diet with 16 or 45 % of energy from corn oil (low n3 PUFA) in comparison with a high-fat diet containing soybean or high-oleic sunflower oil (adequate n3 PUFA) or flaxseed or fish oil (high n3 PUFA) for 11 weeks. High-fat diets, regardless of types of oils, significantly increased body fat mass and body weights compared to the low-fat diet. Adipose fatty acid composition and contents reflected dietary fatty acid profiles. The high-fat fish oil diet significantly increased adiponectin and reduced leptin concentrations in both plasma and adipose tissue; it did not elevate plasma insulin concentration compared to the high-fat corn oil diet. All high-fat diets elevated concentrations of plasminogen activator inhibitor-1 (PAI-1) and monocyte chemoattractant protein-1 (MCP-1) but lowered resistin concentrations in both plasma and adipose tissue. In conclusion, fish oil may be beneficial in improving insulin sensitivity by upregulation of adiponectin and downregulation of leptin production; n3 and n6 PUFA do not play a role at the dietary levels tested in reducing adiposity and production of pro-inflammatory cytokines (leptin, PAI-1, MCP-1 and resistin) and anti-inflammatory cytokine adiponectin.

Obesity represents a major under-recognized preventable risk factor for cancer development and recurrence, including breast cancer (BC). Healthy diet and correct lifestyle play crucial role for the treatment of obesity and for the prevention of BC. Obesity is significantly prevalent in western countries and it contributes to almost 50% of BC in older women. Mechanisms underlying obesity, such as inflammation and insulin resistance, are also involved in BC development. Fatty acids are among the most extensively studied dietary factors, whose changes appear to be closely related with BC risk. Alterations of specific ω-3 polyunsaturated fatty acids (PUFAs), particularly low basal docosahexaenoic acid (DHA) levels, appear to be important in increasing cancer risk and its relapse, influencing its progression and prognosis and affecting the response to treatments. On the other hand, DHA supplementation increases the response to anticancer therapies and reduces the undesired side effects of anticancer therapies. Experimental and clinical evidence shows that higher fish consumption or intake of DHA reduces BC cell growth and its relapse risk. Controversy exists on the potential anticancer effects of marine ω-3 PUFAs and especially DHA, and larger clinical trials appear mandatory to clarify these aspects. The present review article is aimed at exploring the capacity of DHA in controlling obesity-related inflammation and in reducing insulin resistance in BC development, progression, and response to therapies.

An important characteristic of cancer is that the disease can overcome the surveillance of the immune system. A possible explanation for this resistance arises from the ability of tumor cells to block the tumoricidal activity of host immune cells such as natural killer (NK) cells by inducing the localized accumulation of regulatory T (Treg) cells. Evidence exists that components in commonly consumed foods including vitamins A, D, and E, water-soluble constituents of mushrooms, polyphenolics in fruits and vegetables, and n-3 fatty acids in fish oil can modulate NK cell activities, Treg cell properties, and the interactions between those two cell types. Thus, it is extremely important for cancer prevention to understand the involvement of dietary components with the early stage dynamics of interactions among these immune cells. This review addresses the potential significance of diet in supporting the function of NK cells, Treg cells, and the balance between those two cell types, which ultimately results in decreased cancer risk., (Published 2015. This article is a U.S. Government work and is in the public domain in the USA.)

Inflammation is involved in the pathophysiology of many chronic diseases, such as rheumatoid arthritis and neurodegenerative diseases. Several studies have evidenced important anti-inflammatory and immunomodulatory properties of omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs). This review illustrates current knowledge about the efficacy of n-3 LC-PUFAs (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), particularly) in preventing and/or treating several chronic inflammatory conditions (inflammatory bowel diseases and rheumatoid arthritis) as well as their potential benefits on neurodegenerative diseases. It is well established that n-3 LC-PUFAs are substrates for synthesis of novel series of lipid mediators (e.g., resolvins, protectins, and maresins) with potent anti-inflammatory and pro-resolving properties, which have been proposed to partly mediate the protective and beneficial actions of n-3 LC-PUFAs. Here, we briefly summarize current knowledge from preclinical studies analyzing the actions of EPA- and DHA-derived resolvins and protectins on pathophysiological models of rheumatoid arthritis, Alzheimer, and irritable bowel syndrome.

Omega‑3 and ‑6 polyunsaturated fatty acids (PUFAs) can directly or indirectly regulate immune homeostasis via inflammatory pathways, and components of these pathways are crucial targets of microRNAs (miRNAs). However, no study has examined the changes in the miRNA transcriptome during PUFA‑regulated inflammatory processes. Here, we established PUFA diet‑induced autoimmune‑prone (AP) and autoimmune‑averse (AA) rat models, and studied their physical characteristics and immune status. Additionally, miRNA expression patterns in the rat models were compared using microarray assays and bioinformatic methods. A total of 54 miRNAs were differentially expressed in common between the AP and the AA rats, and the changes in rno‑miR‑19b‑3p, ‑146b‑5p and ‑183‑5p expression were validated using stem‑loop reverse transcription‑quantitative polymerase chain reaction. To better understand the mechanisms underlying PUFA‑regulated miRNA changes during inflammation, computational algorithms and biological databases were used to identify the target genes of the three validated miRNAs. Furthermore, Gene Ontology (GO) term annotation and KEGG pathway analyses of the miRNA targets further allowed to explore the potential implication of the miRNAs in inflammatory pathways. The predicted PUFA‑regulated inflammatory pathways included the Toll‑like receptor (TLR), T cell receptor (TCR), NOD‑like receptor (NLR), RIG‑I‑like receptor (RLR), mitogen‑activated protein kinase (MAPK) and the transforming growth factor‑β (TGF‑β) pathway. This study is the first report, to the best of our knowledge, on in vivo comparative profiling of miRNA transcriptomes in PUFA diet‑induced inflammatory rat models using a microarray approach. The results provide a useful resource for future investigation of the role of PUFA‑regulated miRNAs in immune homeostasis.

Omega-3 polyunsaturated fatty acids (w-3 PUFAs) are essential nutrients for human beings and their potential roles against cancer development and progression have become of wide concern recently. Some studies have suggested that perioperative supplementation with omega-3 fatty acids may have beneficial effects in gastrointestinal cancer patients undergoing surgery, while other researchers reported contrary results. This paper reviews recent research to establish therapeutic effects as well as possible underlying mechanisms of ????PUFA actions, and to help explain possible reasons for inconsistent results from different institutions.

Stress-related immune alterations can be consequential for health; they can enhance susceptibility to infectious agents and influence the severity of infectious disease, diminish the strength of immune responses to vaccines, reactivate latent viruses, and slow wound healing. Furthermore, stressful events and negative emotions promote systemic proinflammatory cytokine production while reducing beneficial local production of proinflammatory cytokines at the wound site that are important for wound healing. Dietary omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) also influence systemic inflammation; high proportions of omega-6 to omega-3 boost inflammation, while omega-3 has anti-inflammatory properties. Additionally, the limited evidence thus far suggests that omega-3 PUFA may enhance local inflammatory responses at wound sites. Moreover, an individual's dietary proportion of omega-3 to omega-6 may influence the magnitude of inflammatory responses to stressful events. Thus, wound healing and surgery provide exemplars of how stress and depression can interact with the diet to influence important clinical outcomes., (Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.)

Background: Treatment of symmetrical onychomadesis (symmetrical lupoid onychodystrophy) is a challenging task for dermatologists. The acute phase is characterized by sloughing of claw plates and loose claws have to be removed and secondary infections treated. The goal of long-term treatment is to allow claws to re-grow with normal quality and to achieve life-long lack of recurrence. The aim of this randomized treatment trial was to see if adding fish oil or cyclosporine to a diet rich in omega-3 could improve the treatment outcome of symmetrical onychomadesis in Gordon and English setters. All dogs were fed Eukanuba Veterinary Diets Dermatosis® exclusively during the six month treatment trial. The treatment outcome was measured as the change in number of healthy claws during treatment, as well as the long-term effect on hunting ability and recurrence of onychomadesis. The hypothesis was that cyclosporine provides a stronger and different immune modulating property than fish oil and therefore would give a better treatment outcome in dogs with symmetrical onychomadesis eating a diet rich in omega-3 fatty acids., Results: Six Gordon setters and one English setter were treated with 5 mg/kg cyclosporine once daily for six months and seven Gordon setters were treated with 10 ml Dr Baddaky fish oil® once daily for six months. All dogs were evaluated every month and the numbers of healthy claws were recorded., Conclusion: Cyclosporine and fish oil appeared to be equally effective in treating symmetrical onychomadesis when the dog is fed a diet high in omega-3.

There may be a causal relationship between intake of n-6 polyunsaturated fatty acids (PUFAs) and childhood allergic diseases. This can be explained by plausible biological mechanisms involving eicosanoid mediators produced from the n-6 PUFA arachidonic acid. Long chain n-3 PUFAs are found in fish and fish oils. These fatty acids act to oppose the actions of n-6 PUFAs. Thus, it is considered that n-3 PUFAs will lower the risk of developing allergic diseases. In support of this, protective associations have been reported between maternal fish intake during pregnancy and allergic outcomes in infants and children from those pregnancies. However, studies of fish intake during infancy and childhood and allergic outcomes in those infants or children are inconsistent, although some reported a protective association. Supplementing pregnant women with fish oil can induce immunologic changes in cord blood. This supplementation has been reported in some studies to decrease sensitisation to common food allergens and to lower the prevalence and severity of atopic dermatitis in the first year of life. The protective effect of maternal n-3 PUFAs may last until adolescence of the offspring. Fish oil supplementation in infancy may decrease the risk of developing some manifestations of allergic disease, although this benefit may not persist. Whether fish oil is a useful therapy in children with asthma receiving standard therapy is not clear from studies performed to date and this requires further exploration.

Background: Recently, we have shown that dietary long-chain n-3 polyunsaturated fatty acids (n-3 LCPUFA) largely prevent allergic sensitization in a murine model for cow's milk allergy. The aim of this study was to assess the contribution of regulatory T cells (Treg) in the prevention of food allergy by n-3 LCPUFA., Methods: C3H/HeOuJ female donor mice were fed a control or fish oil diet before and during oral sensitization with cow's milk protein whey. Acute allergic skin response (ASR), anaphylaxis, body temperature, serum immunoglobulins, and mouse mast cell protease-1 (mmcp-1) were assessed. Splenocytes of sham- or whey-sensitized donor mice fed either control or fish oil diet were adoptively transferred to naïve recipient mice. Recipient mice received a whole splenocyte suspension, splenocytes ex vivo depleted of CD25+ cells, or MACS-isolated CD4+ CD25+ Treg. Recipient mice were sham- or whey-sensitized and fed control diet., Results: The ASR as well as whey-specific IgE and whey-specific IgG1 levels were reduced in whey-sensitized donor mice fed the fish oil diet as compared to the control diet. Splenocytes of control-diet-fed whey-sensitized donors transferred immunologic memory. By contrast, splenocytes of fish-oil-fed whey-sensitized - but not sham-sensitized - donors transferred tolerance to recipients as shown by a reduction in ASR and serum mmcp-1, and depletion of CD25+ Treg abrogated this. Transfer of CD25+ Treg confirmed the involvement of Treg in the suppression of allergic sensitization., Conclusions: CD25+ Treg are crucial in whey allergy prevention by n-3 LCPUFA., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The aim of this study was to correlate specific fatty acid profiles of visceral white adipose tissue (WAT) with inflammatory signatures potentially associated with colorectal cancer (CRC)., Methods: Human adipocytes were isolated from biopsies of visceral WAT from 24 subjects subdivided in four groups: normal-weight (BMI 22.0-24.9 Kg/m2) and over-weight/obese (BMI 26.0-40.0 Kg/m2), affected or not by CRC. To define whether obesity and/or CRC affect the inflammatory status of WAT, the activation of the pro-inflammatory STAT3 and the anti-inflammatory PPARγ transcription factors as well as the expression of adiponectin were analyzed by immunoblotting in adipocytes isolated from each group of subjects. Furthermore, to evaluate whether differences in inflammatory WAT environment correlate with specific fatty acid profiles, gas-chromatographic analysis was carried out on WAT collected from all subject categories. Finally, the effect of the ω3 docosahexaenoic acid treatment on the balance between pro- and anti-inflammatory factors in adipocytes was also evaluated., Results: We provide the first evidence for the existence of a pro-inflammatory environment in WAT of CRC patients, as assessed by the up-regulation of STAT3, and the concomitant decrease of PPARγ and adiponectin with respect to healthy subjects. WAT inflammatory status was independent of obesity degree but correlated with a decreased ω3-/ω6-polyunsaturated fatty acid ratio. These observations suggested that qualitative changes, other than quantitative ones, in WAT fatty acid may influence tissue dysfunctions potentially linked to inflammatory conditions. This hypothesis was further supported by the finding that adipocyte treatment with docosahexaenoic acid restored the equilibrium between STAT3 and PPARγ., Conclusion: Our results suggest that adipocyte dysfunctions occur in CRC patients creating a pro-inflammatory environment that might influence cancer development. Furthermore, the protective potential of docosahexaenoic acid in re-establishing the equilibrium between pro- and anti-inflammatory factors might represent a useful tool for preventive and therapeutic strategies.

Inflammation links obesity with the development of insulin resistance. Macrophages and phagocytic immune cells communicate with metabolic tissues to direct an inflammatory response caused by overnutrition and expanding adipose tissue. Marine-derived omega-3 fatty acids, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), modulate inflammatory signalling events, providing various anti-inflammatory and cardioprotective benefits. Moreover, EPA and DHA may improve insulin sensitivity by generating proresolving lipid mediators and promoting alternatively activated macrophages. This review will assess the role of EPA and DHA in ameliorating obesity-induced inflammation, evaluating clinical evidence and mechanisms of action. The pathophysiology of insulin resistance resulting from obesity-induced inflammation will be discussed, highlighting the relationship between metabolism and immunity, and in particular, how EPA and DHA work with both systems to modulate immunometabolic complications and chronic disease., (Copyright © 2013 John Wiley & Sons, Ltd.)

The beneficial health properties of dietary omega-3 polyunsaturated fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have long been known and their metabolic dysfunction has been linked to a range of diseases including various inflammatory disorders, cardiovascular diseases, and cancer. However, the molecular mechanisms underlying their health benefits have remained unclear. Recent technological advances in lipidomic analytical strategies have resulted in the discovery of a range of bioactive mediators derived from EPA and DHA that possess potent anti-inflammatory and pro-resolving properties and that may be responsible, at least in part, for the beneficial effects observed. These mediators include resolvins, protectins and maresins, as well as EPA derivatives of classical arachidonic acid derived eicosanoids, such as prostaglandin E3 . The aim of this review is to provide an overview of the biosynthetic pathways and biological properties of these omega-3 mediators, with a particular focus on the emerging importance of the counter-regulatory role of omega-3 and -6 fatty acids in the spatial and temporal regulation of the inflammatory response. It will also provide an insight into a range of lipidomic approaches, which are currently available to analyse these fatty acids and their metabolites in biological matrices., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Numerous effects of n-3 fatty acids EPA and DHA on functional responses of cells involved in inflammation and immunity have been described. Fatty acid-induced modifications in membrane order and in the availability of substrates for eicosanoid synthesis are long-standing mechanisms that are considered important in explaining the effects observed. More recently, effects on signal transduction pathways and on gene expression profiles have been identified. Over the last 10 years or so, significant advances in understanding the mechanisms of action of n-3 fatty acids have been made. These include the identification of new actions of lipid mediators that were already described and of novel interactions among those mediators and the description of an entirely new family of lipid mediators, resolvins and protectins that have anti-inflammatory actions and are critical to the resolution of inflammation. It is also recognised that EPA and DHA can inhibit activation of the prototypical inflammatory transcription factor NF-κB. Recent studies suggest three alternative mechanisms by which n-3 fatty acids might have this effect. Within T-cells, as well as other cells of relevance to immune and inflammatory responses, EPA and DHA act to disrupt very early events involving formation of the structures termed lipid rafts which bring together various proteins to form an effective signalling platform. In summary, recent research has identified a number of new mechanisms of action that help to explain previously identified effects of n-3 fatty acids on inflammation and immunity.

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are bioactive n-3 long-chain polyunsaturated fatty acids (LCPUFAs) in fish oil that exert immunosuppressive effects. A significant amount of literature shows that n-3 LCPUFAs suppress dendritic cell (DC) function in vitro; however, few studies have determined if the effects are emulated at the animal level. In this study, we first focused on the functional consequences of 5% (weight/weight) fish oil on splenic CD11c(+) DCs. Administration of n-3 LCPUFAs, modelling human pharmacological intake (2% of total kcal from EPA,1·3% from DHA), to C57BL/6 mice for 3 weeks reduced DC surface expression of CD80 by 14% and tumour necrosis factor-α secretion by 29% upon lipopolysaccharide stimulation relative to a control diet. The n-3 LCPUFAs also significantly decreased CD11c(+) surface expression and phagocytosis by 12% compared with the control diet. Antigen presentation studies revealed a 22% decrease in CD69 surface expression on transgenic CD4(+) T lymphocytes activated by DCs from mice fed fish oil. We then determined if the functional changes were mechanistically associated with changes in lipid microdomain clustering or plasma membrane microviscosity with n-3 LCPUFAs, as reported for B and T lymphocytes. Fish oil administration to mice did not influence cholera-toxin induced lipid microdomain clustering or microviscosity, even though EPA and DHA levels were significantly elevated relative to the control diet. Overall, our data show that n-3 LCPUFAs exert immunosuppressive effects on DCs, validating in vitro studies. The results also show that DC microdomain clustering and microviscosity were not changed by the n-3 LCPUFA intervention used in this study., (© 2013 John Wiley & Sons Ltd.)

Omega-3 fatty acids (ω-3 FAs) have potential anti-inflammatory activity in a variety of inflammatory human diseases, but the mechanisms remain poorly understood. Here we show that stimulation of macrophages with ω-3 FAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and other family members, abolished NLRP3 inflammasome activation and inhibited subsequent caspase-1 activation and IL-1β secretion. In addition, G protein-coupled receptor 120 (GPR120) and GPR40 and their downstream scaffold protein β-arrestin-2 were shown to be involved in inflammasome inhibition induced by ω-3 FAs. Importantly, ω-3 FAs also prevented NLRP3 inflammasome-dependent inflammation and metabolic disorder in a high-fat-diet-induced type 2 diabetes model. Our results reveal a mechanism through which ω-3 FAs repress inflammation and prevent inflammation-driven diseases and suggest the potential clinical use of ω-3 FAs in gout, autoinflammatory syndromes, or other NLRP3 inflammasome-driven inflammatory diseases., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Individuals with metabolic syndrome (MetS) have a higher risk of type 2 diabetes and cardiovascular disease, therefore, research has been directed at reducing various components that contribute to MetS and associated metabolic impairments, including chronic low-grade inflammation. Epidemiological, human, animal and cell culture studies provide evidence that dietary n-3 polyunsaturated fatty acids (n-3 PUFA), including alpha-linolenic acid (18:3n-3, ALA), eicosapentaenoic acid (20:5n-3, EPA) and/or docosahexaenoic acid (22:6n-3, DHA) may improve some of the components associated with MetS. The current review will discuss recent evidence from human observational and intervention studies that focused on the effects of ALA, EPA or DHA on inflammatory markers in healthy adults and those with one or more features of MetS. Observational studies in healthy adults support the recommendation that a diet rich in n-3 fatty acids may play a role in preventing and reducing inflammation, whereas intervention studies in healthy adults have yielded inconsistent results. The majority of intervention studies in adults with features of MetS have reported a benefit for some inflammatory measures; however, other studies using high n-3 fatty acid doses and long supplementation periods have reported no effect. Overall, the data reviewed herein support recommendations for regular fatty fish consumption and point toward health benefits in terms of lowering inflammation in adults with one or more features of MetS.

The increasing allergy prevalence in affluent countries may be caused by reduced microbial stimulation and a decreased dietary ω-3/ω-6 long-chain polyunsaturated fatty acid (LCPUFA) ratio, resulting in an abnormal postnatal immune maturation. The timing of allergy-preventive probiotic and ω-3 LCPUFA interventions is critical, as early-life events occurring during critical windows of immune vulnerability can have long-term impact on immune development. The maternal dietary and microbial environment during pregnancy may programme the immune development of the child. Prenatal environmental exposures may alter gene expression via epigenetic mechanisms, aiming to induce physiological adaptations to the anticipated postnatal environment, but potentially also increasing disease susceptibility in the offspring if exposures are mismatched. Although the importance of fetal programming mostly has been studied in cardiovascular and metabolic disease, this hypothesis is also very attractive in the context of environmentally influenced immune-mediated diseases. This review focuses on how prenatal, perinatal or postnatal ω-3 LCPUFA interventions regulate childhood immune and allergy development, and if synergistic effects may be obtained by simultaneous probiotic supplementation. We propose that combined pre- and postnatal preventive measures may be most efficacious. Increasing knowledge on the immunomodulatory effects of prenatal, perinatal and postnatal interventions will help to direct future strategies to combat the allergy epidemic., (© 2012 Blackwell Publishing Ltd.)

Uncontrolled asthma is a major cause of hospitalizations and emergency room visits. Factors including obesity, African ancestry and childhood are associated with increased asthma severity. Considering the high morbidity caused by asthma, relatively few classes of drugs exist to control this common disease. Therefore, new therapeutic strategies may be needed to reduce asthma's impact on public health. Data suggest that a high fat diet that is deficient in omega-3 fatty acids could promote both obesity and excessive inflammation, resulting in greater asthma severity. Small trials with supplemental omega-3 fatty acids have been conducted with encouraging but inconsistent results. The variability in response seen in past trials may be due to the past subjects' genetics (specifically ALOX5 rs59439148) or their particular asthma phenotypes. Therefore, the "Nutrigenetic response to Omega-3 Fatty acids in Obese Asthmatics (NOOA)" trial is currently underway and was designed as a randomized, double-blind, placebo controlled intervention study to determine if supplemental omega-3 fatty acids improves symptoms among obese adolescents and young adults with uncontrolled asthma. Here we report the design and rationale for the NOOA trial. Participants were given either 3.18 g daily of eicosapentaenoic acid and 822 mg daily docosahexaenoic acid, or matched control soy oil, for 24 weeks. Change in the asthma control questionnaire score was the primary outcome. Secondary outcomes included spirometry, impulse oscillometry, exacerbation rate, airway biomarkers, systemic inflammation, leukotriene biosynthesis and T-lymphocyte function. NOOA may lead to a new therapeutic treatment strategy and greater understanding of the mechanistic role of diet in the pathogenesis of asthma., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Recent epidemiological studies highlight the key role of the type of consumed unsaturated fatty acid and the development of ulcerative colitis (UC). We aimed to review the potential mechanisms behind the antiinflammatory effects of unsaturated fatty acids on intestinal inflammation, to discuss their potential limitations, and to propose a new reappraisal of polyunsaturated fatty acids (PUFAs) in the pathophysiology of inflammatory bowel disease (IBD). A literature search using PubMed was carried out to identify relevant studies (basic science, epidemiological studies, or clinical trials) with unsaturated fatty acids and IBD. Only articles published in English were included. IBD patients exhibit an altered lipid metabolism. While in vitro and in vivo studies have demonstrated the antiinflammatory properties of n-3 polyunsaturated fatty acids in experimental models IBD, results of clinical trials have been disappointing. In addition, the impact of fatty acid on innate immunity as an alternative therapeutic approach is explored. This may offer insight into therapeutic avenues for designing n-3 PUFA diet therapy for IBD.

There has been growing interest in the role of n-3 long-chain polyunsaturated fatty acids (LC-PUFA) in the modulation of the immune response during early childhood and whether this may translate to a reduction in childhood allergic disease. Several randomized controlled trials of n-3 LC-PUFA supplementation have been reported, largely involving children who are at high hereditary risk of developing allergies. These studies relatively consistently indicate that supplementation during pregnancy results in fewer children with atopic eczema in early childhood. On the other hand, supplementation studies confined exclusively to the postnatal period have demonstrated mixed results with one trial showing no effect and the other suggesting a transient effect on symptoms of respiratory disease. In summary, supplementation with n-3 LC-PUFA during the perinatal period and before allergic response is established may be a useful strategy to prevent early childhood allergic disease in children at high hereditary risk. Further work is needed to establish the optimal period of supplementation and whether longer term benefits exist., (Copyright © 2013 Nestec Ltd., Vevey/S. Karger AG, Basel.)

Aim: The importance of the alteration of tumor infiltrative lymphocytes (CD4(+), CD8(+), CD16(+), and CD56(+)) in colorectal cancer prognosis is well known. In this study, we analyzed the effect of preoperative immunonutrition and different nutritional models on the clinical condition of colorectal cancer patients., Methods: Twenty-eight colorectal cancer patients were grouped into 4 groups according to their nutrition regimens randomly and were given immunonutrition (IMN), standard enteral (SE), total parental nutrition (TPN), and normal nutrition (NN) regimens, all of which contained the same calorie-nitrogen content within a 7-day preoperative period. All patients had an endoscopic biopsy before and after the regimen, and the lymphocyte population infiltrating mucosal parts of the resected tumor tissue were evaluated. Immunohistochemical analysis of the tissue specimens was performed by staining with antihuman CD4(+), CD8(+), CD16(+), and CD56(+) antibodies., Results: After nutrition, there were significant increases in each of the 4 groups of CD4(+) and CD8(+) cells within the tumor. Comparing the rates of augmentation, the increased rates of the CD8(+) cells infiltrating the tumor after nutrition in the patients who were fed with IMN were significantly more than the ones in other groups (P = .01). CD16(+) cell infiltration was significantly higher in all groups except the SE and IMN groups. The SE group had increased CD56(+) cell infiltration compared with the other groups., Conclusions: In the colorectal cancer patients who had nutrition in the 7-day preoperative period, except for the SE nutrition group, there were significant increases of infiltration of CD56(+) cells at the mucosal part of the tumor tissue within the CD4(+) and CD8(+) cell population. When postnutrition values were compared, there was a marked increase of CD8(+) cells in the IMN group., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Parenteral nutrition (PN) is indispensable for meeting caloric and substrate needs of patients who cannot receive adequate amounts of enteral nutrition; however, PN impairs hepatic immunity. We examined the effects of ω-3 and -6 polyunsaturated fatty acids, added individually to fat-free PN, on hepatic immunity in a murine model. We focused on serum liver enzymes, cytokine production, histopathology, and the outcomes after intraportal bacterial challenge., Methods: Male Institute of Cancer Research mice were randomized into 4 groups; ad libitum chow (CHOW), fat-free PN (FF-PN), PN + fish oil (FO-PN), or PN + safflower oil (SO-PN). After the mice had been fed for 5 days, hepatic mononuclear cells (MNCs) were isolated. The number of MNCs was counted and cytokine production (tumor necrosis factor [TNF]-α and interleukin [IL]-10) by hepatic MNCs in response to lipopolysaccharide (LPS) was measured. Blood samples were analyzed for hepatobiliary biochemical parameters. Moreover, 1.0 × 10(7) pseudomonas aeruginosa were delivered by intraportal injection. Survival and histology were examined., Results: Hepatic MNC numbers were significantly less in the FO-PN and FF-PN than in the CHOW group, whereas the SO-PN group showed moderate recovery of hepatic MNC numbers. The CHOW, FO-PN, and SO-PN groups showed LPS dose-dependent increases in TNF-α levels. These increases were blunted in the FF-PN group. IL-10 levels were increased LPS dose-dependently in the CHOW and FO-PN groups, but no marked changes were observed with LPS stimulation in the SO-PN and FF-PN groups. Plasma levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase were significantly greater in the FF-PN than in the FO- and SO-PN and CHOW groups. The FO-PN group showed significantly improved survival compared with the SO-PN and FF-PN groups, showing essentially no morphologic hepatic abnormalities., Conclusion: Addition of fish oil to PN was advantageous in terms of reversing PN-induced deterioration of hepatic immunity, as reflected by altered cytokine production. Fish oil administration was also useful for preventing PN-induced hepatobiliary dysfunction. These changes seem to result in better survival and to protect against severe tissue damage after intraportal bacterial challenge. This therapy may have the potential to ameliorate PN-induced impairment of host immunity and thereby decrease morbidity and mortality., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Objective: The ω-3 polyunsaturated fatty acids can suppress immune system functions. This property may cause adverse effects by impairing host resistance to infection. The present study focused on estimating the impact of different dietary lipids on the immune system of mice after a secondary infection with Listeria monocytogenes., Methods: BALB/c mice were divided into five dietary groups of olive oil, fish oil, sunflower oil, high-oleic sunflower oil, or low fat that was administered for 8 wk. The mice were immunized with 10(3) colony-forming units. Thirty-eight days later, each mouse was challenged with 10(4) colony-forming units. Mice survival and bacterial clearance from livers and spleens were determined. In addition, cytokine, chemokine, and adhesion molecule productions were quantified from the sera., Results: Survival percentage in mice fed a fish oil diet was 100% and bacterial numbers from spleen were decreased at 72 h. Interleukin-12, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 productions were decreased. Levels of tumor necrosis factor-α and interferon-γ were increased, whereas macrophage inflammatory protein-1α (MIP-1α) production was unaltered., Conclusion: Immune defense in mice fed a fish oil diet was improved after secondary exposure, acquiring an adequate resistance. This result could be attributable to an increase of a T-helper type 1 response., (Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.)

There are two main families of polyunsaturated fatty acids (PUFAs), the n-6 and the n-3 families. It has been suggested that there is a causal relationship between n-6 PUFA intake and allergic disease, and there are biologically plausible mechanisms, involving eicosanoid mediators of the n-6 PUFA arachidonic acid, that could explain this. Fish and fish oils are sources of long-chain n-3 PUFAs and these fatty acids act to oppose the actions of n-6 PUFAs. Thus, it is considered that n-3 PUFAs will protect against atopic sensitization and against the clinical manifestations of atopy. Evidence to examine this has been acquired from epidemiologic studies investigating associations between fish intake in pregnancy, lactation, infancy, and childhood, and atopic outcomes in infants and children and from intervention studies with fish oil supplements in pregnancy, lactation, infancy, and childhood, and atopic outcomes in infants and children. All five epidemiological studies investigating the effect of maternal fish intake during pregnancy on atopic or allergic outcomes in infants/children of those pregnancies concluded protective associations. One study investigating the effects of maternal fish intake during lactation did not observe any significant associations. The evidence from epidemiological studies investigating the effects of fish intake during infancy and childhood on atopic outcomes in those infants or children is inconsistent, although the majority of the studies (nine of 14) showed a protective effect of fish intake during infancy or childhood on atopic outcomes in those infants/children. Fish oil supplementation during pregnancy and lactation or during infancy or childhood results in a higher n-3 PUFA status in the infants or children. Fish oil provision to pregnant women is associated with immunologic changes in cord blood and such changes may persist. Studies performed to date indicate that provision of fish oil during pregnancy may reduce sensitization to common food allergens and reduce prevalence and severity of atopic dermatitis in the first year of life, with a possible persistence until adolescence with a reduction in eczema, hay fever, and asthma. Fish oil provision to infants or children may be associated with immunologic changes in the blood but it is not clear if these are of clinical significance and whether they persist. Fish oil supplementation in infancy may decrease the risk of developing some manifestations of allergic disease, but this benefit may not persist as other factors come into play. It is not clear whether fish oil can be used to treat children with asthma as the two studies conducted to date give divergent results. Further studies of increased long-chain n-3 PUFA provision in during pregnancy, lactation, and infancy are needed to more clearly identify the immunologic and clinical effects in infants and children and to identify protective and therapeutic effects and their persistence.

Objective: The aim of the present paper was to review the literature in order to summarize the effects of marine n-3 fatty acids on circulating inflammatory markers among healthy subjects, subjects with high risk of developing cardiovascular disease (CVD) and in patients with CVD in human intervention studies., Methods: A systematic literature search in PubMed was performed. Intervention studies describing the effects of marine n-3 fatty acids on circulating inflammatory markers in healthy subjects, subjects with high risk of CVD and patients with CVD were included. The following exclusion criteria were used: (1) interventions assessing inflammatory markers with ex vivo methods (2) interventions with children (3) articles describing animal or cell culture studies. Twenty-two articles were included. Additionally, 13 papers from their literature lists were included based on the same inclusion and exclusion criteria as the literature search., Results and Conclusion: Intervention studies with marine n-3 fatty acids administered from either fish or fish oil demonstrate different results on inflammatory markers. No firm conclusion can be drawn about the effect of marine n-3 fatty acids on circulating inflammatory markers in healthy individuals, individuals with high risk of developing CVD or individuals with CVD related diseases.

Background: Long-chain n-3 polyunsaturated fatty acids (PUFAs) have immune regulating and anti-inflammatory effects. However, their role in allergic disease is unclear. Allergic diseases are immunologically heterogeneous, and we hypothesized that n-3 fatty acid composition in serum and breast milk may vary according to clinical manifestations. Further, animal studies have shown reduction of serum-PUFA levels during allergic inflammation., Objective: To investigate fatty acid composition in breast milk and serum from women with different atopic disease manifestations. Secondly, to determine whether low PUFA levels reflected insufficient intakes., Methods: Fatty acids were analysed in breast milk and serum of women with atopic eczema and respiratory allergy (n=16), only respiratory allergy (n=7), as well as healthy women (n=22). Dietary intake of foods expected to affect long-chain n-3 PUFA levels were estimated by food-frequency questionnaire. The fatty acid pattern was related to diagnostic group and intake of relevant food items using a multivariate pattern recognition method (partial least squares projections to latent structures and discriminant analysis). Results Women with a combination of eczema and respiratory allergy had lower breast milk levels of several PUFAs (arachidonic acid, eicosapentaenoic acid, EPA, docosahexaenoic acid, DHA, and docosapentaenoic acid, DPA), and a lower ratio of long-chain n-3 PUFAs/n-6 PUFAs. Their PUFA levels differed not only from that of healthy women, but also from that of women with only respiratory allergy. The latter had a fatty acid pattern similar to that of healthy women. Despite low EPA, DHA and DPA levels women with eczema and respiratory allergy consumed no less fish than did healthy women., Conclusion & Clinical Relevance: Our data suggest that reduced levels of long-chain n-3 fatty acids in serum and breast milk characterize women with extensive allergic disease including eczema, and are not related to low fish intake. Consumption of PUFAs during the allergic process may explain these findings., (© 2011 Blackwell Publishing Ltd.)

Background: Prevalence of atopic disorders has increased rapidly, but aetiological factors responsible for this increase are still largely unknown. Prenatal exposure to a pro-inflammatory fatty acid status is hypothesized although little research has been carried out., Objective: To investigate whether prenatal fatty acid exposures are associated with atopy in childhood., Methods: In the KOALA Birth Cohort Study, maternal blood samples (n=1275) at 34-36 weeks of pregnancy were assayed for n-6 and n-3 long-chain polyunsaturated fatty acids (LCPs). The full spectrum of offspring atopic manifestations (wheeze, asthma, allergic rhinoconjunctivitis, eczema, atopic dermatitis, allergic sensitization, and high total IgE) until the age of 6-7 years was assessed by repeated parental questionnaires and measurements of total and specific IgE. Associations of maternal fatty acid status with child atopic outcomes were analysed using multivariable logistic regression and generalized estimating equations for repeated measurements., Results: High ratio of maternal n-6 vs. n-3 LCPs was associated with a lower risk of eczema in the child (P for trend 0.012). More specifically, we found a decreased risk of eczema in the first 7 months of life with increasing arachidonic acid levels (P for trend 0.013). No associations were found between maternal fatty acids and offspring airway-related atopic manifestations, sensitization, or high total IgE., Conclusion and Clinical Relevance: The development of atopic disorders in early childhood is associated with prenatal exposure to n-6 vs. n-3 fatty acids, but with inconsistencies between different manifestations. Further exploration of associations with maternal diet and genetic variants in genes regulating fatty acid metabolism are required. This study shows that the influence of prenatal exposure to fatty acids on the risk of eczema in the child is limited to the first year of life., (© 2011 Blackwell Publishing Ltd.)

E-series resolvins are antiinflammatory and pro-resolving lipid mediators derived from the ω-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) that actively clear inflammation to promote tissue homeostasis. Aspirin, in addition to exerting antithrombotic actions, also triggers the biosynthesis of these specialized pro-resolving mediators. Here, we used metabolomic profiling to investigate the biosynthesis of E-series resolvins with specific chiral chemistry in serum from human subjects and present evidence for new 18S series resolvins. Aspirin increased endogenous formation of 18S-hydroxyeicosapentaenoate (18S-HEPE) compared with 18R-HEPE, a known resolvin precursor. Human recombinant 5-lipoxygenase used both enantiomers as substrates, and recombinant LTA4 hydrolase (LTA4H) converted chiral 5S(6)-epoxide-containing intermediates to resolvin E1 and 18S-resolvin E1 (RvE1 and 18S-RvE1, respectively). 18S-RvE1 bound to the leukocyte GPCRs ChemR23 and BLT1 with increased affinity and potency compared with the R-epimer, but was more rapidly inactivated than RvE1 by dehydrogenase. Like RvE1, 18S-RvE1 enhanced macrophage phagocytosis of zymosan, E. coli, and apoptotic neutrophils and reduced both neutrophil infiltration and proinflammatory cytokines in murine peritonitis. These results demonstrate two parallel stereospecific pathways in the biosynthesis of E-series resolvins, 18R- and 18S-, which are antiinflammatory, pro-resolving, and non-phlogistic and may contribute to the beneficial actions of aspirin and ω-3 polyunsaturated fatty acids.