Dietary fish oil inhibits antigen-specific murine Th1 cell development by suppression of clonal expansion

To determine the mechanisms by which dietary fish oil (FO) affects antigen-stimulated Th1 cell development, DO11.10 Rag 2(-/-) T cell receptor transgenic mice were fed a control diet (5% corn oil (CO) or a FO diet (1% CO + 4% FO, (n-3) PUFA) for 2 wk. CD4(+) T cells were cultured under neutral or Th1 polarizing conditions. FO feeding suppressed (P < 0.05) ovalbumin peptide-induced proliferation of nonpolarized CD4(+) T cells. Differentiation in vitro to Th1 cells was not affected by dietary FO, as evidenced by similar percentages of KJ1-26(+), IFN-gamma(+), IL-4(-) Th1 cells in cultures from CO-fed (99%) and FO-fed (97%) mice. However, the absolute number of viable Th1 cells in polarized cultures from FO-fed mice was less than half that observed in CO-fed mice (P < 0.05), indicating that FO inhibits in vitro Th1 clonal expansion. The reduced number of Th1 cells in FO cultures was not a result of increased apoptosis, because similar percentages of apoptotic Th1 cells were observed in cultures from FO- and CO-fed mice. IL-2-induced cell proliferation was significantly decreased in polarized Th1 cells from the FO group; however, the suppressed proliferation was not linked to reduced CD25 surface expression on antigen-stimulated CD4(+) T cells. Adoptively transferred CFSE-labeled DO11.10 CD4(+) cells into immunized mice (Th1 polarizing agents) showed that dietary FO reduced (P < 0.05) the number of cell divisions in vivo. These studies suggest that the attenuated inflammatory response which accompanies FO feeding may be explained, at least in part, by suppression of Th1 clonal expansion.     

Fish oil and tocopherol-induced changes in natural killer cell-mediated cytotoxicity and PGE2 synthesis in young and old mice

Natural killer cell (NK) activity decreases and prostaglandin E2 (PGE2) level increases in aged mice. Because PGE2 is involved in control of NK activity this study was conducted to investigate whether or not decreasing PGE2 level by changing the type of dietary fat or increasing the level of vitamin E (vit. E) modulates NK activity of young and old mice. Mice were fed either a corn oil (CO) or a fish oil (FO) diet supplemented with 30 or 500 mg/kg diet of vit. E for 6 wk. To study the effect of vit. E during active immune response and oxidative stress, groups of old mice fed CO and either 30 or 500 mg/kg diet of vit. E were injected with sheep red blood cells (SRBC) prior to assessment of their NK activity. As reported by others regarding mice fed a nonpurified diet, the old mice in all dietary groups had significantly less NK activity and tended to synthesize more PGE2 than young mice. FO-fed mice synthesized less PGE2 than CO-fed mice; however, their NK activity was not higher than that of CO-fed mice. By contrast young mice fed FO had a moderately lower NK activity than those fed CO. Vit. E supplementation did not change NK activity in nonimmunized mice but was effective in preventing SRBC-induced decrease in NK activity of old mice.     

Dietary (n-3) fatty acid and vitamin E interactions in rats: effects on vitamin E status, immune cell prostaglandin E production and primary antibody response.

To examine the interaction between dietary fat and vitamin E at the level of the rat immune system, a 2 x 3 factorial study was designed. Weanling female Sprague Dawley rats were fed for 8-9 wk diets that contained either corn oil (CO diet) or fish oil (FO diet) and one of three levels (30, 300, 900 mg/kg) of all-rac-alpha-tocopheryl acetate. At the lowest level of dietary vitamin E, alpha-tocopherol content of splenocytes from FO-fed rats was approximately 40% lower (P less than 0.05) than in those from CO-fed rats. Supplementation with all-rac-alpha-tocopheryl acetate elevated alpha-tocopherol in splenocytes from FO-fed rats but not in those from CO-fed rats, and reduced the relative proportion of arachidonic acid and eicosapentaenoic acid in the serum of CO-fed and FO-fed rats, respectively. Prostaglandin E production by isolated immune cells was not affected by all-rac-alpha-tocopheryl acetate supplementation. However, feeding the FO diet consistently reduced prostaglandin E synthesis by 70-80% as compared with the CO diet. Antibody production against sheep RBC was highest in rats fed the FO diet supplemented with 900 mg all-rac-alpha-tocopheryl acetate/kg of diet. However, antibody response was not directly correlated to diet-induced changes in immune cell prostaglandin E production or alpha-tocopherol content. Our data suggest that there are significant interactions between vitamin E and (n-3) fatty acids that affect the immune system and that further research in this area is warranted.     

Dietary (n-6) and (n-3) fatty acids and energy restriction modulate mesenteric lymph node lymphocyte function in autoimmune-prone (NZB x NZW)F1 mice

We previously showed that dietary fish oil (FO) and energy restriction (R) have beneficial anti-inflammatory properties in the peripheral blood and spleens of (NZB x NZW)F1 (B/W) lupus-prone mice. Furthermore, unsaturated fatty acids also were shown in the past to influence mesenteric lymph node (MLN) lymphocyte function in healthy young rats. The MLN play a pivotal role in mediating food allergy. To date, the effect of R on intestinal immunity is not well understood; therefore we determined the effect of diet on MLN lymphocyte function. Mice were given either free access to a 5 g/100 g corn oil (CO) or fish oil (FO) diet or the same corn oil (CR) or fish oil (FR) diets restricted to 60% of the intake of the control group. At the age of 4 (young) and 8 (old) mo, MLN lymphocytes were isolated and B- (CD19(+)) and T-lymphocyte subsets (CD4(+) and CD8(+)) were determined by flow cytometry. Additional MLN lymphocytes were placed in culture with or without concanavalin A and culture supernatants collected after 72 h for cytokine and immunoglobulin (Ig) quantitation by ELISA. Aging significantly (P < 0.05) decreased both CD4(+) and CD8(+) T-lymphocytes. Spontaneous and activation-induced interleukin-4 (IL-4), IL-10, and interferon-gamma secretion were greater while IL-2 was lower in CO-fed old mice compared to CO-fed young mice. In contrast, CR or FO alone partially blunted the age-dependent alterations in T-lymphocyte ratios including cytokine and Ig secretion, whereas the FR diet significantly (P < 0.005) normalized the accelerated aging effects on these immune variables. We show for the first time that FR is a far more potent anti-inflammatory therapy than either CR or FO alone in modulating MLN lymphocyte function.     

Effects of dietary omega-3 and omega-6 lipids and vitamin E on serum cytokines, lipid mediators and anti-DNA antibodies in a mouse model for rheumatoid arthritis

OBJECTIVE: Omega-3 (omega-3) fatty acid rich-fish oil (FO) and vitamin E (vit-E) may delay the progress of certain autoimmune diseases. The present study examined the mechanism of action of omega-3 and omega-6 lipids and vit-E on the serum cytokines and lipid mediators in autoimmune-prone MRL/lpr mice (a model for rheumatoid arthritis, RA). The lpr (lymphoproliferative) gene is overexpressed in these mice causing extensive lymphoproliferation, lupus-like symptoms and accelerated aging. METHODS: Weanling female MRL/lpr and congenic control MRL/++ mice were fed 10% corn oil (CO, omega6) or FO-based semipurified diets containing two levels of vitamin E (vit-E-75, I.U. and vit-E-500 I.U./Kg diet) for four months. At the end of the experiment, serum anti-DNA antibodies, cytokines and lipid mediators levels were determined. RESULTS: The appearance of enlarged lymph nodes was delayed in the mice fed FO, and the FO-500 IU vit-E diet offered further protection against enlargement of lymph nodes. The MRL/lpr mice exhibited significantly higher levels of serum anti-dsDNA antibodies. The FO-fed mice had significantly lower serum IL-6, IL-10, IL-12, TNF-alpha, PGE2, TXB2 and LTB4 levels compared with CO-fed mice. In mice fed 500 IU vit-E diets, the serum IL-6, IL-10, IL-12 and TNF-alpha levels were significantly lower and serum IL-1beta was significantly higher compared to 75 IU-vit-E-fed mice in CO/FO or both. The levels of anti-DNA antibodies, IL-4, IL-6, TNF-alpha, IL-10 and IL-12 were higher in the sera of MRL/lpr mice. The FO diet lowered the levels of these cytokines (except IL-4) and lipid mediators. Adding 500 IU of vit-E to the FO diet further lowered the levels of IL-6, IL-10, IL-12, and TNF-alpha. CONCLUSION: It is clear from our observations that the beneficial effects of FO can be enhanced by the addition of 500 IU of vit-E in the diet. The FO diet containing 500 IU of vit-E may specifically modulate the levels of IL-6, IL-10, IL-12 and TNF-alpha and thereby may delay the onset of autoimmunity in the MRL/lpr mouse model. The observations from this study may form a basis for selective nutrition intervention based on specific fatty acids and antioxidants in delaying the progress of RA.     

Involvement of Regulatory T Cells and Their Cytokines Repertoire in Chemopreventive Action of Fish Oil in Experimental Colon Cancer

Gut-associated immune response plays a major role in pathogenesis of many diseases including cancer. Modulation of intestinal immune response via dietary components might influence prognosis of colon carcinoma. This study was designed to evaluate the effect of differential ratios of fish oil (FO) and corn oil (CO) on T cells in experimental colon carcinoma. Male Wistar rats were divided into six groups: Group I received purified diet while Groups II and III received purified diet supplemented with FO:CO(1:1) and FO:CO(2.5:1), respectively. These were further subdivided into controls and treated with ethylenediaminetetraacetic acid (EDTA) or N,N'-dimethylhydrazine dihydrochloride (DMH), respectively. Regulatory T cells (natural and induced; nTregs and iTregs), helper T cells, surface markers (CD28, αβTCR, γδTCR), and intracellular cytokines in CD4⁺ cells were analyzed in colonic intraepithelial lymphocytes (IELs). DMH treatment led to a significant decrease in nTregs and increase in iTregs. Treatment with FO/CO resulted in an increase in both Tregs as compared to DMH group. Intracellular interleukin (IL)-10 and IL-6 levels increased on DMH treatment, while FO/CO treatment decreased their levels. DMH treatment led to elevation of CD4⁺ cells expressing surface markers in comparison to control group. This expression decreased considerably with FO/CO. FO modulates immune response against colon cancer by altering Tregs and their cytokine repertoire.     

Ethanol effects on lipid peroxidation and glutathione-mediated defense in rat small intestine: Role of dietary fats

The effect of ethanol feeding for 5 weeks on lipid peroxidation status of small intestine was studied in rats maintained on either a rat pellet (RP) or a semisynthetic diet containing coconut oil (CCO), corn oil (CO), or fish oil (FO). Highest rate of iron/ascorbate-induced lipid peroxidation was observed in intestinal mucosa of FO-fed rats, which was further elevated (p < 0.05) upon ethanol administration. Purified brush borders from all the ethanol-treated dietary groups were more susceptible to iron-induced lipid peroxidation. Level of nonprotein thiols was increased by ethanol feeding to rats given CO or FO. FO-fed rats exhibited increased activities of glutathione reductase (GR), glutathione-S-transferase (GST), and catalase (Cat). Glutathione peroxidase (GPx) was the lowest in the CCO group. Ethanol-treated FO group exhibited increased GST and GPx activities compared to controls, whereas in rats fed the RP or CO diet, ethanol feeding significantly decreased GST activity. GR and Cat activities were not affected under these conditions. Thus, ethanol exposes the small intestinal mucosa to oxidative stress. The effects were more pronounced in rats fed n-3 fatty acid-rich (FO) diet. The corresponding rise in GPx and GST levels may reflect the adaptive changes in intestine.     

不同类型多不饱和脂肪酸对产蛋鸡免疫功能及肝脏脂质过氧化的影响

目的 :　研究不同类型多不饱和脂肪酸 (PUFA)对产蛋鸡体液免疫功能、淋巴细胞前列腺素 E2 合成及机体脂质过氧化的影响。方法 :　 360只 60 w龄的海兰褐产蛋鸡随机分为 1 0个处理组 ,各组试验日粮为 :对照组 (不添加油脂 ) ;鱼油三个添加水平 (1 %、3%、5% ) ;胡麻油三个添加水平 (2 %、4%、6% ) ;玉米油三个添加水平 (2 %、4%、6% )。结果 :　添加不饱和油脂均可以提高血清抗体效价 ,其中鱼油和胡麻油添加组与对照组相比差异显著 (P<0 .0 5) ;添加玉米油组的血清溶菌酶含量显著低于其它油脂添加组和对照组 (P<0 .0 1 ) ;添加鱼油和胡麻油组的外周血淋巴细胞 PGE2 的合成量显著低于添加玉米油组 (P<0 .0 5) ;不同水平多不饱和脂肪酸的添加影响了肝脏组织脂质过氧化分解产物丙二醛 (MDA)的含量 ,随着不饱和油脂添加量的提高 ,MDA含量呈上升的趋势 ,但是 6%玉米油组显著低于鱼油 5%添加组 (P<0 .0 5)。结论 :　在本试验条件下 ,产蛋鸡日粮中添加不同类型的多不饱和脂肪酸可以影响动物的免疫反应和肝组织脂质过氧化作用     

Influence of dietary conjugated linoleic Acid and fat source on body fat and apoptosis in mice

OBJECTIVE: To determine whether altered dietary essential fatty acid (linoleic and arachidonic acid) concentrations alter sensitivity to conjugated linoleic acid (CLA)-induced body fat loss or DNA fragmentation. RESEARCH METHODS AND PROCEDURES: Mice were fed diets containing soy oil (control), coconut oil [essential fatty acid deficient (EFAD)], or fish oil (FO) for 42 days, and then diets were supplemented with a mixture of CLA isomers (0.5% of the diet) for 14 days. Body fat index, fat pad and liver weights, DNA fragmentation in adipose tissue, and fatty acid profiles of adipose tissue were determined. RESULTS: The EFAD diet decreased (p < 0.05) linoleic and arachidonic acid in mouse adipose tissue but did not affect body fat. Dietary CLA caused a reduction (p < 0.05) in body fat. Mice fed the EFAD diet and then supplemented with CLA exhibited a greater reduction (p < 0.001) in body fat (20.21% vs. 6.94% in EFAD and EFAD + CLA-fed mice, respectively) compared with mice fed soy oil. Dietary FO decreased linoleic acid and increased arachidonic acid in mouse adipose tissue. Mice fed FO or CLA were leaner (p < 0.05) than control mice. FO + CLA-fed mice did not differ in body fat compared with FO-fed mice. Adipose tissue apoptosis was increased (p < 0.001) in CLA-supplemented mice and was not affected by fat source. DISCUSSION: Reductions in linoleic acid concentration made mice more sensitive to CLA-induced body fat loss only when arachidonic acid concentrations were also reduced. Dietary essential fatty acids did not affect CLA-induced DNA fragmentation.     

Dietary (n-3) polyunsaturated fatty acids modulate murine Th1/Th2 balance toward the Th2 pole by suppression of Th1 development

We showed that dietary long-chain (n-3) PUFAs present in fish oil (FO) affect CD4(+) T cell proliferation and cytokine production in C57BL/6 mice. To test the hypothesis that the anti-inflammatory effect of dietary (n-3) PUFAs could be due to the indirect suppression of T helper (Th)1 cells by cross-regulation of enhanced Th2 activation, mice were fed a wash-out control diet [5% corn oil (CO), (n-6) PUFA] for 1 wk, followed by the control diet or a fish oil diet [1% CO + 4% FO, (n-3) PUFA] for 2 wk. Splenic CD4+ T cells were cultured under both neutral and Th2 polarizing conditions for 2 d. Cells were reactivated and analyzed for interleukin-4 and interferon-gamma by intracellular cytokine staining. Dietary fish oil significantly increased the percentage of Th2 polarized cells and suppressed Th1 cell frequency under neutral conditions. However, under Th2 polarizing conditions, although the suppression of Th1 cells was maintained in FO-fed mice, no effect was observed in Th2 cells. Dietary fish oil increased the Th2/Th1 ratio in the presence of homologous mouse serum under both neutral (P = 0.0009) and Th2 polarizing conditions (P = 0.0185). The FO diet did not significantly affect proliferation under Th2 polarizing conditions. Thus, the anti-inflammatory effects of FO may be explained in part by a shift in the Th1/Th2 balance, due to the direct suppression of Th1 development, and not by enhancement of the propensity of CD4+ T cells to be polarized toward a Th2 phenotype, at least in vitro.     

Echium Oil Reduces Plasma Triglycerides by Increasing Intravascular Lipolysis in apoB100-Only Low Density Lipoprotein (LDL) Receptor Knockout Mice

Echium oil (EO), which is enriched in SDA (18:4 n-3), reduces plasma triglyceride (TG) concentrations in humans and mice. We compared mechanisms by which EO and fish oil (FO) reduce plasma TG concentrations in mildly hypertriglyceridemic male apoB100-only LDLrKO mice. Mice were fed one of three atherogenic diets containing 0.2% cholesterol and palm oil (PO; 20%), EO (10% EO + 10% PO), or FO (10% FO + 10% PO). Livers from PO- and EO-fed mice had similar TG and cholesteryl ester (CE) content, which was significantly higher than in FO-fed mice. Plasma TG secretion was reduced in FO vs. EO-fed mice. Plasma very low density lipoprotein (VLDL) particle size was ordered: PO (63 ± 4 nm) > EO (55 ± 3 nm) > FO (40 ± 2 nm). Post-heparin lipolytic activity was similar among groups, but TG hydrolysis by purified lipoprotein lipase was significantly greater for EO and FO VLDL compared to PO VLDL. Removal of VLDL tracer from plasma was marginally faster in EO vs. PO fed mice. Our results suggest that EO reduces plasma TG primarily through increased intravascular lipolysis of TG and VLDL clearance. Finally, EO may substitute for FO to reduce plasma TG concentrations, but not hepatic steatosis in this mouse model.     

Does Oil Rich in Alpha-Linolenic Fatty Acid Cause the Same Immune Modulation as Fish Oil in Walker 256 Tumor-Bearing Rats?

Objective: Polyunsaturated fatty acids n-3 (PUFA n-3) have shown effects in reducing tumor growth, in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) abundantly present in fish oil (FO). When these fatty acids are provided in the diet, they alter the functions of the cells, particularly in tumor and immune cells. However, the effects of α-linolenic fatty acid (ALA), which is the precursor of EPA and DHA, are controversial. Thus, our objective was to test the effect of this parental fatty acid. Methods: Non-tumor-bearing and tumor-bearing Wistar rats (70 days) were supplemented with 1 g/kg body weight of FO or Oro Inca® (OI) oil (rich in ALA). Immune cells function, proliferation, cytokine production, and subpopulation profile were evaluated. Results: We have shown that innate immune cells enhanced phagocytosis capacity, and increased processing and elimination of antigens. Moreover, there was a decrease in production of pro-inflammatory cytokines (tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6)) by macrophages. Lymphocytes showed decreased proliferation capacity, increased cluster of differentiation 8 (CD8⁺) subpopulation, and increased TNF-α production. Conclusions: Oil rich in ALA caused similar immune modulation in cancer when compared with FO.     

Effects of dietary lipid composition and inulin-type fructans on mineral bioavailability in growing rats

ObjectiveThis study reports the effects of feeding with a combination of inulin-type fructans (ITF) and fish oil (FO) on mineral absorption and bioavailability as part of a semipurified diet offered to rats.MethodsMale Wistar rats (n = 24) were fed a 15% lipid diet (soybean oil [SO] or a 1:0.3 fish:soybean oil mixture [FSO]) and diets containing the same sources of lipids supplemented with 10% ITF (Raftilose Synergy 1) ad libitum for 15 d. Feces and urine were collected for mineral analyses during the last 5 d of the test period. Fatty acid composition was determined in liver and cecal mucosa homogenates. Liver and bone mineral analyses were performed by atomic absorption spectrophotometry. Bone biomechanical analyses were evaluated by a 3-point bending test.ResultsCompared with the controls, ITF-fed rats had enlarged ceca and a significant decrease in cecal content pH (P < 0.001). The apparent mineral absorption was improved in these rats, and this effect was enhanced by dietary combination with FO for all minerals except for magnesium. Addition of ITF to the diet resulted in higher bone mineral content (calcium and zinc) and bone strength, but increased bone mineral content was only statistically significant in FO-fed animals. A decrease in liver iron stores (P = 0.015) was observed in rats fed FO, considering that ITF consumption returned to levels comparable to the SO control group.ConclusionThese findings confirm the positive influence of ITF on mineral bioavailability, which was potentiated by addition of FO to the diet.     

Examination of host immune resistance against Listeria monocytogenes infection in cyclophosphamide-treated mice after dietary lipid administration

BACKGROUND & AIMS: Despite the beneficial effects in the resolution of inflammatory disorders due to their immunosuppressive properties, n-3 polyunsaturated fatty acids are associated with a reduction of immune resistance to some microorganisms. Here, we examine the influence of different dietary lipids on host immune resistance against Listeria monocytogenes in mice treated with cyclophosphamide (CPA). METHODS: Balb/c mice were fed one of four diets, which contained either olive oil (OO), fish oil (FO), hydrogenated coconut oil (HCO) or low fat (LF) for 4 weeks. Subsequently, mice were treated with CPA or PBS, prior to L. monocytogenes infection. Splenocyte proliferation, survival analysis, counts of viable bacteria from spleens and livers, and measurement of pro-inflammatory cytokine levels were determined. RESULTS: The FO-rich diet reduced survival, particularly in CPA-treated mice. CPA was responsible for a significant increase of viable bacteria recovery from spleens and livers within each group fed high fat diets, which was aggravated in mice fed an FO diet. In addition, a significant increase of both TNF-alpha and IL-12p70 levels was detected in this group. These results may acquire a crucial relevance in clinical nutrition, particularly when FO diets are administered to immunocompromised patients. CONCLUSIONS: The mechanism(s) that impair(s) the elimination of L. monocytogenes could be associated with a low mitogen-stimulated splenocyte proliferation, and with an alteration of pro-inflammatory cytokine production. The application of the neutropenic agent CPA moderately aggravates the immunosuppressive state mainly in FO-fed animals.     

HER-2/neu (657-665) represents an immunogenic epitope of HER-2/neu oncoprotein with potent antitumor properties

The HER-2/neu oncoprotein is a promising cancer vaccine target. We describe herein a novel HLA-A2.1-restricted epitope, encompassing amino acids 657-665 (AVVGILLVV), which is naturally presented by human breast and ovarian cell lines. HER-2/neu(657-665), [HER-2(9₆₅₇)], binds with high affinity to HLA-A2.1 molecules as revealed by a prediction algorithm (SYFPEITHI) and in functional assays. This peptide was found to be immunogenic in HLA-A2.1 transgenic (HHD) mice inducing peptide-specific CTL, which responded with increased IFNγ production, degranulation, and in vitro as well as in vivo cytotoxicity. Most important, HER-2(9₆₅₇) functioned as a therapeutic vaccine by enabling HHD mice to reject established transplantable tumors. Cured mice resisted tumor growth when re-challenged with the same tumor, demonstrating the capacity of HER-2(9₆₅₇) to generate tumor-specific memory immune response. Finally, this peptide was also found to be immunogenic in PBMCs from HLA-A2.1⁺ patients with HER-2/neu⁺ breast cancer. Our data encourage further exploitation of HER-2(9₆₅₇) as a promising candidate for peptide-based cancer vaccines.     

Krill oil versus fish oil in modulation of inflammation and lipid metabolism in mice transgenic for TNF-α

Purpose

Biological effects of marine oils, fish oil (FO) and krill oil (KO), are mostly attributed to the high content of n-3 polyunsaturated fatty acids (n-3 PUFAs), predominantly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The study was aimed to investigate the influence of FO and KO on lipid homeostasis and inflammation in an animal model of persistent low-grade exposure to human tumor necrosis factor α (hTNF-α) and to evaluate whether these effects depend on the structural forms of EPA and DHA [triacylglycerols (TAG) vs. phospholipids].

Methods

Male C57BL/6 hTNF-α mice were fed for 6 weeks a high-fat control diet (24.50 % total fats, w/w) or high-fat diets containing either FO or KO at similar doses of n-3 PUFAs (EPA: 5.23 vs. 5.39 wt%, DHA: 2.82 vs. 2.36 wt% of total fatty acids).

Results

We found that KO, containing bioactive n-3 PUFAs in the form of phospholipids, was capable of modulating lipid metabolism by lowering plasma levels of TAG and cholesterol and stimulating the mitochondrial and peroxisomal fatty acid β-oxidation, as well as improving the overall carnitine turnover. Though the administration of FO was not as effective as KO in the lowering of plasma TAG, FO significantly improved the levels of all cholesterol classes in plasma. Except from the increase in the levels of IL-17 in FO-fed mice and a trend to decrease in MCP-1 levels in KO-fed animals, the levels of pro-inflammatory cytokines were not substantially different between treatment groups.

Conclusion

Our findings demonstrate that FO and KO are comparable dietary sources of n-3 PUFAs. However, when quantitatively similar doses of n-3 PUFAs are administered, KO seems to have a greater potential to promote lipid catabolism. The effect of dietary oils on the levels of inflammatory markers in hTNF-α transgenic mice fed a high-fat diet needs further investigations.     

Splenic and Intestinal Lymphocyte Proliferation Response in Mice Fed Milk or Yogurt and Challenged with Salmonella Typhimurium

Two groups of 4-5 week old DBA/2J Nil mice were put on either a yogurt-based (n = 33) or a milk-based (n = 32) diet for a period of 4 weeks. At the end of the feeding trial one sub group of mice each from the two dietary groups was sacrificed for assessment of immune response. The remaining mice were challenged intragastrically with 2 × 10¹⁰ live Salmonella typhimurium organisms and continued on their respective diets for 8 days after which they were also sacrificed. The immune response was measured by tritiated thymidine uptake by splenic or intestinal lymphocytes in response to the mitogens concanavalin A (Con A), Phytohaemaggutinin (PHA), and Lipopolysaccharide from Escherichia coli (LPS). Serum Immunoglobulin A levels were also estimated. Feed efficiency, measured as weight gain per unit energy intake, was significantly higher for the yogurt diet than for the milk diet. The mitogenic response of splenic and intestinal lymphocytes in the two groups of unchallenged mice was not different. In the Salmonella-challenged mice the stimulation index (SI) of splenic lymphocytes from yogurt-fed mice (mean ± SD) was significantly higher (P = 0.001) in response to Con A (24.71 ± 3.40) than that of milk-fed mice (15.85 ± 2.09). Further, in these mice the SI of intestinal lymphocytes from yogurt-fed mice was higher than that of milk-fed mice in response to Con A (7.35 ± 0.61 vs 5.65 ± 0.78, P = 0.016) and LPS (9.04 ± 0.93 vs 6.15 ± 1.32, P = 0.016). Serum IgA levels in Salmonella-challenged mice were significantly higher 8 days after the challenge in the yogurt-fed group than in the milk-fed group (P < 0.001). The experiments indicate an improvement in local gastrointestinal as well as systemic immunity on a yogurt diet as compared to a milk diet.     

Dietary Canola Oil Suppressed Growth of Implanted MDA-MB 231 Human Breast Tumors in Nude Mice

Long chain omega 3 (n-3) fatty acids, eicosapentaenoic (EPA) and/or docosahexaenoic acid (DHA), have been shown to suppress growth of most cancer cells. In vivo, alpha linolenic acid (ALA, 18:3n-3) can be converted to EPA or DHA. We hypothesized that substituting canola oil (10% ALA) for the corn oil (1% ALA) in the diet of cancer bearing mice would slow tumor growth by increasing n-3 fatty acids in the diet. Sixty nude mice received MDA-MB 231 human breast cancer cells and were fed a diet containing 8% w/w corn oil until the mean tumor volume was 60 mm ³ . The dietary fat of half of the tumor bearing mice was then changed to 8% w/w canola oil. Compared to mice that consumed the corn oil containing diet, the mice that consumed the canola oil containing diet had significantly more EPA and DHA in both tumors and livers, and the mean tumor growth rate and cell proliferation in the tumor were significantly slower (P < 0.05). About 25 days after diet change, mice that consumed the corn oil diet stopped gaining weight, whereas the mice that consumed the canola oil diet continued normal weight gain. Use of canola oil instead of corn oil in the diet may be a reasonable means to increase consumption of n-3 fatty acids with potential significance for slowing growth of residual cancer cells in cancer survivors.     

Effects of ω‐3 Polyunsaturated Fatty Acids on the Homeostasis of CD4+ T Cells and Lung Injury in Mice With Polymicrobial Sepsis

Background: Sepsis is a common cause of death in critically ill patients. An overwhelming inflammatory response and imbalance of helper T (Th) cells and regulatory T (Treg) cells are thought to be involved in the progression of sepsis. ω‐3 Polyunsaturated fatty acids (PUFAs) were found to have anti‐inflammatory and immunomodulatory properties. This study investigated the effects of ω‐3 PUFAs on the balance of Th subsets, Treg cells, and the inflammatory response in septic mice. Methods: Mice were randomly assigned to soybean oil (SO) and fish oil (FO) groups. The 2 groups received an identical nutrient distribution except for the sources of the fat. The SO group was fed soybean oil, while part of the soybean oil was replaced by fish oil in the FO group. The FO group had an ω‐6/ω‐3 PUFA ratio of 2:1. After feeding the diets for 3 weeks, sepsis was induced by cecal ligation and puncture (CLP), and mice were sacrificed on days 0, 1, and 3. Results: Compared with the SO group, the FO group had lower inflammatory mediator levels in the plasma and peritoneal lavage fluid after CLP. Also, the FO group had lower Th1, Th2, and Th17 percentages and a higher Th1/Th2 ratio in blood. In lung tissues, neutrophil infiltration was reduced, whereas peroxisome proliferator–activated receptor γ expression was upregulated. Conclusions: A fish oil diet with an ω‐6/ω‐3 PUFA ratio of 2:1 may elicit more balanced Th polarization, alleviate inflammatory responses, and attenuate lung injury in CLP‐induced sepsis.     

Energy-restricted diets result in higher numbers of CD4, CD8, immunoglobulins (A, M, and G), and CD45RA cells in spleen and CD4, immunoglobulin A, and CD45RA cells in colonic lamina propria of rats

Dietary energy restriction (ER) offers certain health benefits, particularly when ER is controlled through manipulation of dietary fats. Our hypothesis is that cellular immunity is modulated by dietary ER. Furthermore, we believe that the immune response may differ between spleen and colon because their lymphatic and vascular organization is different. The objective of the study was to test this hypothesis by determining the effects of dietary ER through manipulation of energy intake from high-fat (HF) diets on the expression and frequency of the CD4⁺ (T-helper/T-inducer) and CD8⁺ (T-cytotoxic/T-suppressor) cells, CD45RA (B-cell–specific marker), and immunoglobulins (Ig) A-, G-, and M-bearing cells in spleen and colon in rats by immunohistochemical method. Rats fed the HF diet had a significantly (P < .05) reduced number of immune cells as compared with those fed ER diets. Energy-restricted diet–fed rats showed higher (P < .05) numbers of CD4⁺, CD8⁺, IgA, IgM, IgG, and CD45RA cells in spleen and CD4⁺, IgA, and CD45RA cells in colonic lamina propria. The IgA-containing cells were markedly higher in the colon compared with the spleen. No change occurred in the number of IgM- and IgG-containing cells in colonic tissues between groups, except for the 20% ER group where IgM-labeled cells were higher (P < .05) compared with HF and 40% ER groups. These findings suggest that ER may modulate adaptive immune function and that CD4⁺ and IgA cells may serve as biological indicators for dietary energy-modulated immunoresponse in spleen and colon, respectively.