Dietary source of polyunsaturated fatty acids influences cell cytotoxicity in broiler chickens.

The current study aims to investigate the effects of dietary source of n-3 polyunsaturated fatty acids (PUFA) on immune response in broiler chickens, represented by cytotoxic cell activity. A total of 255 one-day-old male Cobb 500 broiler chickens were fed on fish oil (FO)-, flaxseed oil-enriched diets at 50 and 19 g/kg, respectively, in addition to the soybean-based control diet. At slaughter, samples of blood and spleen were harvested from 20 birds/treatment (n = 20). The immune tissues' fatty acid profile was analyzed by gas chromatography, and the cytotoxic cell activity was investigated. The results showed that supplementing broiler chickens with diets rich in n-3 PUFA had a substantial effect on the broiler immune tissues' fatty acid profile. Cytotoxic cell activity was significantly higher in splenocytes and peripheral blood mononuclear cells (PBMCs) from broilers fed flaxseed oil than those provided FO and the soybean control diet. These results suggest that flaxseed oil may be used to enrich chickens with n-3 PUFA and improve the immune status of chicken flocks to resist diseases.

Chenopodium Quinoa and Salvia Hispanica Provide Immunonutritional Agonists to Ameliorate Hepatocarcinoma Severity under a High-Fat Diet.

Complex interactions between immunonutritional agonist and high fat intake (HFD), the immune system and finally gut microbiota are important determinants of hepatocarcinoma (HCC) severity. The ability of immunonutritional agonists to modulate major aspects such as liver innate immunity and inflammation and alterations in major lipids profile as well as gut microbiota during HCC development is poorly understood. 1H NMR has been employed to assess imbalances in saturated fatty acids, MUFA and PUFA, which were associated to variations in iron homeostasis. These effects were dependent on the botanical nature (Chenopodium quinoa vs. Salvia hispanica L.) of the compounds. The results showed that immunonutritional agonists' promoted resistance to hepatocarcinogenesis under pro-tumorigenic inflammation reflected, at a different extent, in increased proportions of F4/80+ cells in injured livers as well as positive trends of accumulated immune mediators (CD68/CD206 ratio) in intestinal tissue. Administration of all immunonutritional agonists caused similar variations of fecal microbiota, towards a lower obesity-inducing potential than animals only fed a HFD. Modulation of Firmicutes to Bacteroidetes contents restored the induction of microbial metabolites to improve epithelial barrier function, showing an association with liver saturated fatty acids and the MUFA and PUFA fractions. Collectively, these data provide novel findings supporting beneficial immunometabolic effects targeting hepatocarcinogenesis, influencing innate immunity within the gut-liver axis, and providing novel insights into their immunomodulatory activity.

The Influence of Dietary Fatty Acids on Immune Responses.

Diet-derived fatty acids (FAs) are essential sources of energy and fundamental structural components of cells. They also play important roles in the modulation of immune responses in health and disease. Saturated and unsaturated FAs influence the effector and regulatory functions of innate and adaptive immune cells by changing membrane composition and fluidity and by acting through specific receptors. Impaired balance of saturated/unsaturated FAs, as well as n-6/n-3 polyunsaturated FAs has significant consequences on immune system homeostasis, contributing to the development of many allergic, autoimmune, and metabolic diseases. In this paper, we discuss up-to-date knowledge and the clinical relevance of the influence of dietary FAs on the biology, homeostasis, and functions of epithelial cells, macrophages, dendritic cells, neutrophils, innate lymphoid cells, T cells and B cells. Additionally, we review the effects of dietary FAs on the pathogenesis of many diseases, including asthma, allergic rhinitis, food allergy, atopic dermatitis, rheumatoid arthritis, multiple sclerosis as well as type 1 and 2 diabetes.

Current understanding of the role of dietary lipids in the pathophysiology of psoriasis.

Dietary lipids are fundamental nutrients for human health. They are typically composed of various long-chain fatty acids which include saturated fatty acids (SFAs) and unsaturated fatty acids (UFAs). UFAs are further classified into several groups, such as omega-3 polyunsaturated fatty acids (PUFAs) and omega-6 PUFAs, depending on their chemical structure. Epidemiological studies have suggested the involvement of dietary lipids in the progression or regulation of psoriasis, a common chronic inflammatory skin disease induced via the IL-23/IL-17 axis. Although the underlying mechanisms by which dietary lipids regulate psoriasis have remained unclear, with the advancement of experimental techniques and the development of psoriasis mouse models, various possible mechanisms have been proposed. For example, SFAs may facilitate psoriatic dermatitis by causing activation of the inflammasome in keratinocytes and macrophages or by inducing IL-17-producing cells, such as Th17 and IL-17-producing γδ T cells in the skin, while omega-3 PUFAs may play inhibitory roles by suppressing Th17 differentiation. In this review, we summarize current data on the roles of dietary lipids in the development of psoriasis as revealed by mouse studies, and we discuss potential therapeutic strategies for psoriasis from the perspective of dietary lipids.

Dietary Lipid Type, Rather Than Total Number of Calories, Alters Outcomes of Enteric Infection in Mice.

Dietary lipids modulate immunity, yet the means by which specific fatty acids affect infectious disease susceptibility remains unclear. Deciphering lipid-induced immunity is critical to understanding the balance required for protecting against pathogens while avoiding chronic inflammatory diseases. To understand how specific lipids alter susceptibility to enteric infection, we fed mice isocaloric, high-fat diets composed of corn oil (rich in n-6 polyunsaturated fatty acids [n-6 PUFAs]), olive oil (rich in monounsaturated fatty acids), or milk fat (rich in saturated fatty acids) with or without fish oil (rich in n-3 PUFAs). After 5 weeks of dietary intervention, mice were challenged with Citrobacter rodentium, and pathological responses were assessed. Olive oil diets resulted in little colonic pathology associated with intestinal alkaline phosphatase, a mucosal defense factor that detoxifies lipopolysaccharide. In contrast, while both corn oil and milk fat diets resulted in inflammation-induced colonic damage, only milk fat induced compensatory protective responses, including short chain fatty acid production. Fish oil combined with milk fat, unlike unsaturated lipid diets, had a protective effect associated with intestinal alkaline phosphatase activity. Overall, these results reveal that dietary lipid type, independent of the total number of calories associated with the dietary lipid, influences the susceptibility to enteric damage and the benefits of fish oil during infection.

Increased intake of vegetable oil rich in n-6 PUFA enhances allergic symptoms and prevents oral tolerance induction in whey-allergic mice.

Increased intake of vegetable oils rich in n-6 PUFA, including soyabean oil, has been associated with an increase in allergic disease. The present study aimed to determine the effect of an increasing dose of dietary vegetable oil on allergic outcomes in mice. To study this, mice received a 7 v. 10 % soyabean oil diet before and during oral sensitisation with whey or whey hyperimmune serum transfer. Another group of mice received partial whey hydrolysate (pWH) while being fed the diets before oral sensitisation. The acute allergic skin response, serum Ig level, mouse mast cell protease-1 (mMCP-1) concentration and/or splenic T-cell percentages were determined upon whey challenge. When the diets were provided before and during oral sensitisation, the acute allergic skin response was increased in mice fed the 10 % soyabean oil diet compared with the 7 % soyabean oil diet. Whey IgE and IgG1 levels remained unaltered, whereas mMCP-1 levels increased in mice fed the 10 % soyabean oil diet. Furthermore, allergic symptoms were increased in naive mice fed the 10 % soyabean oil diet and sensitised with whey hyperimmune serum. In addition to enhancing the mast cell response, the 10 % soyabean oil diet increased the percentage of activated Th1 and Th2 cells as well as increased the ratios of Th2:regulatory T cells and Th2:Th1 when compared with the 7 % soyabean oil diet. Oral tolerance induction by pWH was abrogated in mice fed the 10 % soyabean oil diet compared with those fed the 7 % soyabean oil diet during pretreatment with pWH. In conclusion, increased intake of soyabean oil rich in n-6 PUFA suppresses tolerance induction by pWH and enhances the severity of the allergic effector response in whey-allergic mice. Dietary vegetable oils rich in n-6 PUFA may enhance the susceptibility to develop or sustain food allergy.

Dietary n-3 LC-PUFA during the perinatal period as a strategy to minimize childhood allergic disease.

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.

Modulation of the IgM gene expression and IgM immunoreactive cell distribution by the nutritional background in gilthead sea bream (Sparus aurata) challenged with Enteromyxum leei (Myxozoa).

The aim of the present work was to determine if a plant protein-based diet containing vegetable oils (VO) as the major lipid source could alter the distribution of IgM immunoreactive cells (IRCs) and the IgM expression pattern in the intestine and haematopoietic tissues of gilthead sea bream (GSB) (Sparus aurata) challenged with the myxosporean Enteromyxum leei. In a first trial (T1), GSB fed for 9 months either a fish oil (FO) diet or a blend of VO at 66% of replacement (66VO diet) was challenged by exposure to parasite-contaminated water effluent. All fish were periodically and non-lethally sampled to know their infection status. After 102 days of exposure, samples of intestine and head kidney were obtained for IgM expression and immunohistochemical detection (IHC). Additional samples of spleen were taken for IHC. Fish were categorized as control (C, not exposed), and early (E), or late (L) infected. The 66VO diet had no effect on the number of IgM-IRCs in any of the tissues or on IgM expression in C fish, whereas the infection with E. leei had a strong effect on the intestine. A combined time-diet effect was also observed, since the highest expression and IRCs values were registered in the posterior intestine (Pi) of E-66VO fish. A positive correlation was found between IgM expression and the presence of IgM-IRCs in the Pi. The effect of the time of infection was studied more in detail in a second trial (T2) in which samples of Pi were taken at 0, 24, 51, 91 and 133 days after exposure to the parasite. A significant increase of the IgM expression was detected only in parasitized fish, and very late after exposure. These results show that the duration of the exposure to the parasite is the most determinant factor for the observed intestinal IgM increased phenotype which gets magnified by the feeding of a high VO-based diet.

Acquired resistance to Listeria monocytogenes during a secondary infection in a murine model fed dietary lipids.

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.

Total substitution of fish oil by vegetable oils in gilthead sea bream (Sparus aurata) diets: effects on hepatic Mx expression and some immune parameters.

The use of vegetable oils in fish nutrition has been extensively studied; and recent work has focused attention on replacing fish oil with alternative fatty acid sources and their effect on the immune system. However, little is known about the effect of these oils on immune parameters such as the fish interferon system. In this study we evaluate the effect of two vegetable oils (linseed and soybean) on gilthead sea bream Mx expression and other innate immune parameters. Experimental diets were formulated where fish oil was totally replaced by vegetable oils or for a mixture of them (50% linseed and 50% soybean). Another diet prepared with pure fish oil was used as a control. Two experiments were carried out in order to evaluate growth, feed utilization, serum alternative complement pathway activity, serum lysozyme and phagocytic activity of head kidney leucocytes as well as Mx expression in the liver. In the first experiment fish were fed with experimental diets for 6 months and then, growth and feed utilization as well as immune parameters were analyzed. In the second experiment, fish from the previous feeding trial were injected with either a sub-lethal dose of Photobacterium damselae subsp. piscicida (94/99) or a synthetic dsRNA (Poly I:C) in order to stimulate an Mx response. The results show that total substitution of fish oil by vegetable oils decreased the growth of gilthead sea bream juveniles. Furthermore, both phagocytic activity and serum alternative complement pathway activity were significantly reduced by the inclusion of either vegetable oil individually in the sea bream diets, but the diet with mixed vegetable oils had no significant effect. There was no effect on serum lysozyme levels but the basal constitutive levels of Mx transcript expression in the liver were elevated in the fish fed the vegetable oil diets. The time-course of the Mx response to injection of Poly I:C was shorter in the fish fed the fish oil diet and the fish fed the diet based on a mixture of both vegetable oils showed a faster Mx response to bacterial injection. Following stimulation with Poly I:C or PDP the fish fed the vegetable oil based diets still maintained higher basal levels of hepatic Mx expression than the fish fed the fish oil diet which returned to undetectable levels.

Nutrition in inflammatory bowel disease.

PURPOSE OF REVIEW: Nutrition plays a significant role in the pathogenesis and treatment of the two major forms of inflammatory bowel disease: Crohn's disease and ulcerative colitis. In addition, patients with inflammatory bowel disease are often found to have nutrient deficiencies at the time of diagnosis, whereas others develop features of malnutrition over the course of their illness. Therefore, an understanding of the relationship between nutrients and inflammatory bowel disease is important if these patients are to receive optimal care. RECENT FINDINGS: Epidemiologic and basic research has helped to shed light on the interaction between diet and the pathogenesis of inflammatory bowel disease. Numerous clinical trials utilizing various types of lipids, including fish oil and short chain fatty acids, suggest that fats play an important role in the inflammatory response that characterizes inflammatory bowel disease. Vitamins and other micronutrients involved in nutrient metabolism and modulation of oxidative stress are also considered in this review. SUMMARY: This update discusses nutritional issues that can be used to help prevent and treat nutrient deficiencies and ameliorate disease activity in individuals with inflammatory bowel disease.

A mechanistic approach to understanding conjugated linoleic acid's role in inflammation using murine models of rheumatoid arthritis.

A naturally occurring fatty acid, conjugated linoleic acid (CLA), reduces immune-induced TNF and inducible cyclooxygenase (COX-2) expression; key mediators of inflammation in rheumatoid arthritis (RA). On the basis of previous work, it was hypothesized that dietary CLA would act as an anti-inflammatory agent in select animal models of RA. In the collagen antibody-induced arthritis (CAIA) model, mice fed CLA (mixed isomers of c9, t11, and t10, c12-CLA) for 3 wk before anticollagen antibody injection had reduced lipopolysaccharide-induced plasma TNF levels and had arthritic scores that were 60% of mice fed corn oil (CO). In the collagen-induced arthritis (CIA) model, mice fed mixed isomers of CLA for 21 days before immunization had lower IgG(1) titers, earlier signs of joint inflammation, but similar arthritis scores compared with CO fed mice during the remaining 70-day post-injection period. Beginning on day 80 to 133, CLA-fed mice had arthritic scores 70% that of the CO-fed mice. In a second CIA experiment, CLA was fed only after the booster injection. Plasma IgG(1) levels were not reduced and arthritis onset was delayed 4 days in CLA-fed mice compared with the CO-fed mice. Peak arthritis score was similar between CLA and CO-fed mice from day 35 to 56. Because CLA reduced inflammation in the CAIA model, delayed onset of arthritis in the CIA model (CIA experiment 2) and reduced arthritis score after day 80 in the CIA model (CIA experiment 1), we concluded that dietary CLA exhibited anti-inflammatory activity that was dependent on antibody.

Assessment of interleukin-12, gamma interferon, and tumor necrosis factor alpha secretion in sera from mice fed with dietary lipids during different stages of Listeria monocytogenes infection.

Recent experimental observations have determined that long-chain n-3 polyunsaturated fatty acids suppress immune functions and are involved in the reduction of infectious disease resistance. BALB/c mice were fed for 4 weeks with one of four diets containing either olive oil (OO), fish oil (FO), hydrogenated coconut oil, or a low fat level. Interleukin-12p70 (IL-12p70), gamma interferon (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) production in the sera of mice fed these diets and challenged with Listeria monocytogenes were determined by enzyme-linked immunosorbent assay. In addition, bacterial counts from spleens of mice were carried out at 24, 72, or 96 h of infection. Here, we quantified an initial diminution of production of both IL-12p70 and IFN-gamma, which appear to play an important role in the reduction of host resistance to L. monocytogenes infection. In addition, an efficient elimination of L. monocytogenes was observed in spleens of mice fed a diet containing OO at 96 h of infection, despite reductions in IL-12p70 and TNF-alpha production, suggesting an improvement of immune resistance. Overall, our results indicate that the initial reduction of both IL-12 and IFN-gamma production before L. monocytogenes infection represents the most relevant event that corroborates the impairment of immune resistance by n-3 polyunsaturated fatty acids during the different stages of infection. However, we speculate that the modulation of other cytokines must be also involved in this response, because the alteration of cytokine production in mice fed an FO diet in a late phase of L. monocytogenes infection was similar to that in mice fed OO, whereas the ability to eliminate this bacterium from the spleen was improved in the latter group.

[Food allergy: effect of proteins-lipids and proteins-polysaccharides interactions]. / Allergénicité alimentaire: importance des interactions protéines-lipides et protéines-polysaccharides.

The most widely used ingredients in food formulation are proteins, lipids and polysaccharides. Proteins-lipids and proteins-polysaccharides interactions play a key role in the structure, stability, sensorial and nutritional properties of formulated foods. The objective of the present study is to highlight the importance of proteins-lipids and proteins-polysaccharides interactions, on the immuno-reactivity of allergenic proteins. Two models have been studied, on the one hand refined and not refined oils (soya and sunflower) and soya lecithin, on the other hand mixtures based on peanut proteins and polysaccharides (arabic gum, pectin, xylan). STUDY OF OILS: We have extracted proteins, using a PBS buffer, from refined and not refined oils from soya, sunflower and from soya lecithin, determined protein concentrations and identified allergenic proteins using SDS-PAGE electrophoresis and immuno-blotting. Phospholipids are determined by atomic absorption spectrometry. The protein determination and SDS-PAGE show the presence of a higher amount of proteins in not refined oils and lecithin as compared to refined oils. An important amount of proteins associated to phospholipids are eliminated by degumming on the form of lecithin. On the other hand, residual proteins from refined oils are accompanied by phospholipids. Immuno-blots reveal the presence of a 56 kDa allergen in oils issued from soya seeds and soya lecithin, and the presence of a 67 kDa allergen in oils issued from sunflower seeds. We conclude that the presence or elimination of proteins, especially allergens from oils is linked to amphiphilic association to phospholipids. STUDY OF PEANUT PROTEINS-POLYSACCHARIDES MIXTURES: We have digested in vitro proteins in a dialysis bag using a multi-enzymatic method and characterized proteins and peptides using SDS-PAGE electrophoresis and immuno-blotting. Our results confirm that peanut proteins alone are digested by proteases and that a number of large peptides still have epitopes recognized by anti-peanut proteins antibodies. Our results also show that the presence of polysaccharides changes the peptidic profile after digestion and that, depending on the polysaccharide type, smaller or larger peptides can be obtained in the dialysis bag. Smaller peptides are obtained using pectin whereas larger peptides are obtained using arabic gum and xylan. In the latter case, an increasing amount of peptides reacts to antibodies. Our first observations clearly show the need to better understand modifications of proteins allergenicity induced by the presence of other ingredients such as polysaccharides and lipids, in relation to technological treatments.

Effects of oils rich in eicosapentaenoic and docosahexaenoic acids on immune cell composition and function in healthy humans.

BACKGROUND: Supplementation of the diet with fish oil, which is rich in the long-chain n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is reported to decrease several markers of immune function. However, whether EPA, DHA, or a combination of the 2 exerts these immunomodulatory effects is unclear. OBJECTIVE: The objective of the study was to determine the effects of supplementation with an EPA-rich or DHA-rich oil on a range of immune outcomes representing key functions of human neutrophils, monocytes, and lymphocytes in healthy humans. DESIGN: In a placebo-controlled, double-blind, parallel study, 42 healthy subjects were randomly allocated to receive supplementation with either placebo (olive oil), EPA (4.7 g/d), or DHA (4.9 g/d) for 4 wk. Blood samples were taken before and after supplementation. RESULTS: The fatty acid composition of plasma phospholipids and neutrophils was dramatically altered by supplementation with EPA or DHA, and the effects of EPA differed notably from those of DHA. DHA supplementation decreased T lymphocyte activation, as assessed by expression of CD69, whereas EPA supplementation had no significant effect. Neither the EPA-rich oil nor the DHA-rich oil had any significant effect on monocyte or neutrophil phagocytosis or on cytokine production or adhesion molecule expression by peripheral blood mononuclear cells. CONCLUSIONS: Supplementation with DHA, but not with EPA, suppresses T lymphocyte activation, as assessed by expression of CD69. EPA alone does not, therefore, influence CD69 expression. No other marker of immune function assessed in this study was significantly affected by either EPA or DHA.

Dietary fatty acids and immune reactions in synovial tissue.

Inflammation of the synovial membrane in rheumatoid arthritis is mediated by specialized cells necessary for immune response. The most prominent features are the accumulation of mononuclear phagocytes, lymphocytes and leukocytes in the proliferating tissue. Pro-inflammatory and proliferative signals are transmitted to the bone marrow and to the synovial membrane. The result is a monoclonal stimulation of specific cell lines, and synovial proliferation in the inflamed joint. Angiogenesis, synovial hypertrophy, and increased perfusion facilitate the accumulation of inflammatory cells. Components of the autoimmune reaction are described in the international system of classification, the CD-System (cluster of differentiation). Pro-inflammatory signals are mediated by metabolites of arachidonic acid. Prostaglandins, leukotrienes, lipoxines and hydroxy fatty acids, derived from this PUFA, stimulate the formation and the activity of adhesion molecules (integrines), cytokines (gamma-interferon, interleukin-1, interleukin-6, tumor-necrosis factor), chemokines (interleukine-8, macrophage-chemotactic peptide, RANTES and colony -stimulating factors ((CSF, granulocytes/ monocytes-CSF, Multi-CSF (= IL-3)). Dietary means to mitigate inflammation comprise reduction of arachidonic acid, and increased intake of eicosapentaenoic acid and antioxidants. In the literature 12 randomized, placebo-controlled double-blind studies, fulfilling GCP-criteria, demonstrate a moderate but consistent improvement of clinical findings and laboratory parameters in patients with RA. A dose-response relationship was established up to an daily dose of 2.6 gram fish oil, equivalent to about 1.6 gram EPA. In these experiments EPA was the omega-3 fatty acid responsible for improvement, with distinct effects on inhibition of cytokines formation (IL-1 to IL-6, IL-8, TFN-alpha, GM-CSF), decreased induction of proinflammatory adhesion molecules (selectines, intercellular adhesions molecule-1 (ICAM-1)), and degrading enzymes (e.g. phospholipase A2, cyclooxygenase-2, inducible NO-synthetase). Only one study reports the relevance of the background diet. From this study it became apparent that reduction of dietary arachidonic acid improves the incorporation and the clinical benefit of EPA.

The role of dietary long-chain n-3 fatty acids in anti-cancer immune defense and R3230AC mammary tumor growth in rats: influence of diet fat composition.

We determined if long-chain n-3 fatty acids fed as part of a: (1) high polyunsaturated fat diet (currently recommended by several health agencies) or (2) low polyunsaturated fat diet (representative of that consumed by a large segment of the North American population) improved antitumor immune defense and inhibited tumor growth. Rats were fed one of four semi-purified diets (20% w/w fat) for 21 days pre- and 17 days post- R3230AC mammary tumor implantation. The polyunsaturated to saturated fatty acid (P/S) ratio was either 1 (high P/S diet) or 0.35 (low P/S diet). At each P/S ratio, diets provided long-chain n-3 fatty acids at 0 or 5% w/w of total fat. Long-chain n-3 fatty acids fed in a high P/S diet did not affect tumor growth or host immune responses. In contrast, feeding long-chain n-3 fatty acids in a low P/S diet increased natural killer cell cytotoxicity, splenocyte nitric oxide and interleukin-2 production, and the proportion of activated (CD25+) CD8+ and CD28+ cells, but did not significantly inhibit tumor growth. For both P/S diets, tumor cells from rats fed long-chain n-3 fatty acids had a higher n-3 content and n-3/n-6 ratio in phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol. Furthermore, the magnitude of increase in n-3 fatty acid incorporation into tumor phospholipids was greater when fed in a low P/S diet. We demonstrated that the dietary P/S ratio significantly influences the effect of long-chain n-3 fatty acids on host immune responses and n-3 fatty acid incorporation into tumor cells. These findings warrant further consideration when designing dietary recommendations.