High α-linolenic acid and fish oil ingestion promotes ovulation to the same extent in rats

Prostaglandins (PG) have a regulatory influence on ovulation. α-Linolenic acid (ALA) vs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) differently influence PG biosynthesis. Whereas high EPA/DHA reduces PGE₂, enhancing ovulation, we hypothesized that ALA would not affect ovulation. Our objective was to determine the effect of low and high ALA intake vs EPA/DHA on ovarian phospholipids, ovulation, and PG synthesis in rats. Following 27 days on diet and ovulation induction, ovaries were isolated and analyzed in 22 pups per diet. Ovarian phospholipid (n-3) polyunsaturated fatty acid (PUFA) incorporation increased with EPA/DHA ingestion. With significant ovarian (n-3) PUFA or EPA (P < .05) enrichment in the high–n-3 PUFA diets, ova release increased. Although high ALA did not enrich total (n-3), it increased ova release and tissue EPA over low ALA or control. Dietary EPA/DHA more effectively reduced ovarian arachidonic acid levels than dietary ALA. Dietary ALA increased PGF and very high intake reduced PGE, whereas EPA/DHA did not alter PGE or PGF. Enhanced ova release with high (n-3) PUFA intake may be induced via multiple mechanisms including reduced ovarian arachidonic acid. Significant ovarian retention of EPA and DHA enhanced ovulation with unchanged total PGE and PGF. Lack of change in PGE may have resulted from reduced PGE₂ combined with increased PGE₃. When EPA alone was elevated, PGE was reduced, whereas PGF was increased. Results indicate that very high ALA intake enhances ovulation similar to very high EPA/DHA ingestion, an effect potentially mediated via similar patterns of PGF₂α and PGE₂ synthesis.     

Docosahexaenoic acid and eicosapentaenoic acid affect ovarian prostaglandin levels differently in rats

Prostaglandins (PGs) play a key role in the regulation of ovulation. Typically, ingestion of the long-chain n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) has been found to decrease, whereas arachidonic acid (ARA) increases PG biosynthesis in most systems. We hypothesized that DHA and EPA would decrease ovarian PGE₂, enhancing ovulation, with combined EPA and DHA having the greatest effect, whereas ARA would increase PGE₂, suppressing ovulation. Our objective was to determine how 0.3-g/100-g diet DHA and EPA alone or combined, or ARA would affect tissue composition, ovulation, and PG synthesis in rats. After 27 days on diet and ovulation induction, ovaries were isolated and analyzed from 22 pups per diet. Eicosapentaenoic acid alone reduced ovarian n-6 PUFA attributable to reduced ARA incorporation. Arachidonic acid ingestion reduced and EPA enhanced ovarian n-3 PUFA to levels above what was seen with DHA or DHA/EPA combinations. Docosahexaenoic acid alone increased total PGE 1.5-fold over control, whereas neither differed from the remaining treatments. Increased total PGE with DHA was attributable to elevated PGE₃ with PGE₂ unchanged by diet, and PGE₃ only increased with DHA ingestion alone. Total PGF differed from control with the highest DHA intake, alone or combined with EPA, or with ARA ingestion (P < .05). Increased PGF with DHA was attributable to increased PGF_3α. Experimental diets did not alter ovulation from control. Results indicate that DHA and EPA consumption at human achievable doses differently alters ovarian phospholipids and PGs associated with ovulation with potential for significant 3-series PG without significantly perturbing ovulation.     

Mitogen stimulation of lymphocytes in CBA mice exposed to lead and cadmium.

CBA mice were exposed to lead acetate or cadmium chloride in drinking water for 10 weeks. Selected groups of these animals were also injected with Bacillus Calmette-Guerin (BCG) during exposure to the metals. The ability of mitogens concanavalin A (Con A) and lipopolysaccharide (LPS) as well as purified protein derivative (PPD) to induce proliferation of splenic lymphocytes was assessed. In general, lead tended to inhibit lymphocyte proliferation by LPS and PPD while cadmium potentiated blastogenesis by these mitogens. The two larger doses of cadmium, 30 and 300 ppm, resulted in intense proliferation which was significant (P < 0.05) for the non-BCG, 300-ppm cadmium group. However, 3 ppm cadmium reduced the lymphocyte response to LPS and PPD which was significant (P < 0.05) for the non-BCG-injected mice. Lead and cadmium did not significantly affect the response of lymphocyte proliferation by Con A. Group variation and interpretation of data are discussed.     

Effects of macrocyclic trichothecene mycotoxins on the murine immune system

Macrocyclic trichothecenes are a class of mycotoxins, some of which exhibit substantial antileukemic properties. These compounds vary in their toxicity by approximately 100 fold and are suspected immunotoxins. We studied 11 of these mycotoxins: roritoxin B, myrotoxin B, roridin A, verrucarin A, 16-hydroxyverrucarin A, verrucarin J, baccharinoid B12, roridin D, roridin E, baccharinoid B4 and baccharinoid B5 for their immunotoxicity in CD-1 mice. An equitoxic dose was prepared in 1% DMSO in saline and administered i.p. at half the LD₅₀. Organ weights, WBC, RBC, differentials of blood cell counts, blastogenesis of splenic lymphocytes in response to concanavalin A (Con A), lipopolysaccharide (LPS), phytohemagglutinin (PHA) and pokeweed mitogen (PWM), and mixed lymphocyte reaction (MLR) were studied on day 4 after administration of each mycotoxin. Organ weights showed significant differences between the controls and the baccharinoids with a decrease in spleen weight in baccharinoid B12 and an increased liver weight in B4 and B5 treated animals. Administration of myrotoxin B, roridin A, verrucarin J and roridin E had total WBC counts statistically different from controls, while mice administered myrotoxin B showed a decrease in numbers of RBC. Differentials of WBC were unremarkable regardless of the mycotoxin. Roritoxin B and baccharinoid B5 increased Con A stimulation of splenic lymphocytes. Roridin A and baccharinoid B12 increased LPS stimulation of splenic lymphocytes while baccharinoid B5 decreased the LPS response. Stimulation of splenic lymphocytes with PHA was significantly increased by roridin A and baccharinoid B5. Stimulation of splenic lymphocytes with PWM was not altered significantly by any mycotoxin. The baccharinoids B12 and B4 showed significant increases of T cell proliferation in the MLR. Antibody production evaluated by the sheep red blood cell (SRBC) hemolytic-plaque assay indicated none of the mycotoxins gave a statistically different response. However, anti-SRBC antibodies evaluated by the enzyme-linked immunosorbent assay, were significantly decreased in mice administered roridin D and E and baccharinoid B5.Supported in part by Public Health Service grants-ES 07097 and CA 25967.     

Impact of Korean pine nut oil on weight gain and immune responses in high-fat diet-induced obese mice

Korean pine nut oil (PNO) has been reported to have favorable effects on lipid metabolism and appetite control. We investigated whether PNO consumption could influence weight gain, and whether the PNO-induced effect would result in an improvement of immune function in high-fat diet (HFD)-induced obese mice. C57BL/6 mice were fed control diets with 10% energy fat from either PNO or soybean oil (SBO), or HFDs with 45% energy fat from 10% PNO or SBO and 35% lard, 20% PNO or SBO and 25% lard, or 30% PNO or SBO and 15% lard for 12 weeks. The proliferative responses of splenocytes upon stimulation with concanavalin A (Con A) or lipopolysaccharide (LPS), Con A-stimulated production of interleukin (IL)-2 and interferon (IFN)-γ, and LPS-stimulated production of IL-6, IL-1β, and prostaglandin E₂ (PGE₂) by splenocytes were determined. Consumption of HFDs containing PNO resulted in significantly less weight gain (17% less, P < 0.001), and lower weight gain was mainly due to less white adipose tissue (18% less, P = 0.001). The reduction in weight gain did not result in the overall enhancement in splenocyte proliferation. Overall, PNO consumption resulted in a higher production of IL-1β (P = 0.04). Replacement of SBO with PNO had no effect on the production of IL-2, IFN-γ, IL-6, or PGE₂ in mice fed with either the control diets or HFDs. In conclusion, consumption of PNO reduced weight gain in mice fed with HFD, but this effect did not result in the overall improvement in immune responses.     

The effect of high lipid diet on in vitro prostaglandin E2 and thromboxane B2 production by splenic macrophages

Feeding animals a diet high in linoleic acid for 7 days had no effect on the in vitro production of PGE2 by unstimulated macrophages. Feeding animals the high linoleic acid diet for 30 days greatly increased the production of PGE2 by macrophages when they were unstimulated, but decreased the production of PGE2 when they were stimulated with LPS. Feeding animals a diet high in linoleic acid for 30 days increased the production of TxB2 by macrophages when they were unstimulated, but decreased the production of TxB2 when they were stimulated. Normal, unstimulated splenic macrophages produced almost 80 times more TxB2 than PGE2. However, when the macrophages were stimulated the ratio decreased to six or less because of a greater increase in PGE2 production. The high linoleic acid diet did not inhibit the antibody dependent cellular cytotoxicity of macrophages.     

6种多糖对小鼠免疫细胞活性作用的比较研究

目的探讨香菇多糖等6种多糖(LPS)对小鼠免疫细胞活性的作用,并比较其免疫调节作用的途径和强度。方法6种多糖体外作用于小鼠免疫细胞,MTT法测脾淋巴细胞增殖活性,ELISA法测LPS诱导的脾淋巴细胞分泌IgG水平,吞噬中性红法测腹腔巨噬细胞吞噬功能,乳酸脱氢酶测定法测脾NK细胞活性。结果协同ConA促进脾淋巴细胞增殖作用强弱依次是香菇多糖、灵芝多糖、黄芪多糖、人参多糖、海带多糖和地衣多糖(P<0.05);协同LPS促进脾淋巴细胞增殖作用依次是灵芝多糖、香菇多糖、地衣多糖、黄芪多糖和人参多糖(P<0.05);促进脾淋巴细胞分泌IgG的依次是黄芪多糖、灵芝多糖、人参多糖、地衣多糖和>香菇多糖(P<0.05);增强腹腔巨噬细胞吞噬活性的依次是黄芪多糖、地衣多糖、香菇多糖、海带多糖、灵芝多糖和人参多糖(P<0.05);增强脾NK细胞活性的依次是黄芪多糖、地衣多糖、海带多糖、香菇多糖和灵芝多糖(P<0.05)。结论6种多糖作用的机制和效果各不相同,香菇多糖、灵芝多糖、地衣多糖和黄芪多糖分别在增强细胞免疫、体液免疫和非特异免疫的某一功能上效果显著,可以适宜的剂量比例组合成复合多糖。     

Manifestations of cellular immunity in the rat after prolonged asbestos inhalation. II. Alveolar macrophage-induced splenic lymphocyte proliferation

The present study has shown that alveolar macrophages from asbestos-exposed rats (dusted macrophages) can induce the proliferation of autologous splenic lymphocytes (dusted lymphocytes) as well as the proliferation of syngeneic lymphocytes from control nonexposed rats (control lymphocytes). Significant lymphoproliferation did not occur when alveolar macrophages from control rats (control macrophages) were cocultured with control or dusted splenic lymphocytes for similar periods of time (72 or 96 hr). The activation of control lymphocytes by dusted macrophages was similar, in some respects, to the lymphoproliferative response evoked by sodium periodate-treated control macrophages, since both these reactions peaked at 72 hr and were abolished by treatment of the macrophages with the reducing agent, l-cysteine. This periodate-like response produced by dusted macrophages appears to result from aldehyde-like modifications on the macrophage cell membrane. l-Cysteine treatment did not, however, affect the blastogenic response induced by dusted macrophages on dusted lymphocytes, which peaked at 96 hr. Since the in vitro addition of crocidolite to cell cultures did not trigger lymphoproliferation, these collective findings suggest the expression of asbestos-related antigen-like determinants on the surface of dusted macrophages. We conclude that the proliferative reactions induced in splenic lymphocytes by dusted macrophages were a consequence of two different phenomena: a periodate-like effect (noted in control lymphocytes) and an effect produced by a putative asbestos-related, macrophage-associated antigen (observed in dusted lymphocytes).     

Effects of Dietary Fat and Endurance Exercise on Plasma Cortisol,Prostaglandin E2, Interferon-γ and Lipid Peroxides in Runners

Objective: Exercise and the neuroendocrine and oxidative stress it elicits on immune function is modulated by dietary fat intake. The effects of increasing dietary fat on endurance exercise-induced alterations (80% of V?O_2max for 2 hours) in the plasma levels of cortisol and prostaglandin E₂ (PGE₂), interferon-γ (IFN-γ) and lipid peroxides were investigated. As higher levels of cortisol, PGE₂ and lipid peroxides could be immunosuppressive, the effects of different levels of dietary fat on these measures in runners were determined.

Methods: Healthy trained runners (males and females) consumed serially 15% fat diet (of daily energy), 30% fat diet and 40% fat diets for four weeks each. In the last week of each diet period the subjects ran to exhaustion at 80% of their V?O_2max and blood was drawn pre- and post-run. Cortisol, IFN-γ, PGE₂ and lipid peroxides were determined using standard techniques.

Results: Pre-exercise levels of plasma cortisol were elevated, IFN-γ was unchanged and PGE₂ and lipid peroxides decreased on the 40%F diet compared to 30%F and 15%F. Post-exercise levels of plasma cortisol (p < 0.004), PGE₂ (p < 0.0057) and lipid peroxide levels increased (p < 0.0001) after endurance exercise on all diets. The rates of increase of plasma cortisol levels during exercise were similar on all three diets. Although absolute cortisol levels were higher in the high fat group, the rate of increase of plasma cortisol level during exercise was similar on each diet. The dietary fat levels did not affect IFN-γ, however, PGE₂ and lipid peroxides decreased with increasing fat at baseline at 40%F level (p < 0.01; 30%F vs. 40%F: p < 0.002; 15%F vs. 40%F: p < 0.007).

Conclusions: Data from the present study suggest that higher levels of fat in the diet, up to 40%, increase endurance running time without adverse effects on plasma cortisol, IFN-γ, and lipid peroxide levels.     

Avenanthramides Inhibit Proliferation of Human Colon Cancer Cell Lines In Vitro

A high intake of whole grain foods is associated with reduced risk of colon cancer, but the mechanism underlying this protection has yet to be elucidated. Chronic inflammation and associated cyclooxygenase-2 (COX-2) expression in the colon epithelium are causally related to epithelial carcinogenesis, proliferation, and tumor growth. We examined the effect of avenanthramides (Avns), unique polyphenols from oats with anti-inflammatory properties, on COX-2 expression in macrophages, colon cancer cell lines, and on proliferation of human colon cancer cell lines. We found that Avns-enriched extract of oats (AvExO) had no effect on COX-2 expression, but it did inhibit COX enzyme activity and prostaglandin E₂ (PGE₂) production in lipopolysaccharide-stimulated mouse peritoneal macrophages. Avns (AvExO, Avn-C, and the methylated form of Avn-C (CH3-Avn-C)) significantly inhibited cell proliferation of both COX-2-positive HT29, Caco-2, and LS174T, and COX-2-negative HCT116 human colon cancer cell lines, CH3-Avn-C being the most potent. However, Avns had no effect on COX-2 expression and PGE₂ production in Caco-2 and HT29 colon cancer cells. These results indicate that the inhibitory effect of Avns on colon cancer cell proliferation may be independent of COX-2 expression and PGE₂ production. Thus, Avns might reduce colon cancer risk through inhibition of macrophage PGE₂ production and non-COX-related antiproliferative effects in colon cancer cells. Interestingly, Avns had no effect on cell viability of confluence-induced differentiated Caco-2 cells, which display the characteristics of normal colonic epithelial cells. Our results suggest that the consumption of oats and oat bran may reduce the risk of colon cancer not only because of their high fiber content but also due to Avns, which attenuate proliferation of colonic cancer cells.     

Dietary supplementation with gamma-linolenic acid or fish oil decreases T lymphocyte proliferation in healthy older humans.

Animal and human studies have shown that greatly increasing the amounts of flax seed oil [rich in the (n-3) polyunsaturated fatty acid (PUFA) alpha-linolenic acid (ALNA)] or fish oil [FO; rich in the long chain (n-3) PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] in the diet can decrease mitogen-stimulated lymphocyte proliferation. The objective of this study was to determine the effect of dietary supplementation with moderate levels of ALNA, gamma-linolenic acid (GLA), arachidonic acid (ARA), DHA or FO on the proliferation of mitogen-stimulated human peripheral blood mononuclear cells (PBMC) and on the production of cytokines by those cells. The study was randomized, placebo-controlled, double-blinded and parallel. Healthy subjects ages 55-75 y consumed nine capsules/d for 12 wk; the capsules contained placebo oil (an 80:20 mix of palm and sunflower seed oils) or blends of placebo oil with oils rich in ALNA, GLA, ARA or DHA or FO. Subjects in these groups consumed 2 g of ALNA or 770 mg of GLA or 680 mg of ARA or 720 mg of DHA or 1 g of EPA plus DHA (720 mg of EPA + 280 mg of DHA) daily from the capsules. Total fat intake from the capsules was 4 g/d. The fatty acid composition of PBMC phospholipids was significantly changed in the GLA, ARA, DHA and FO groups. Lymphocyte proliferation was not significantly affected by the placebo, ALNA, ARA or DHA treatments. GLA and FO caused a significant decrease (up to 65%) in lymphocyte proliferation. This decrease was partly reversed by 4 wk after stopping the supplementation. None of the treatments affected the production of interleukin-2 or interferon-gamma by PBMC and none of the treatments affected the number or proportion of T or B lymphocytes, helper or cytotoxic T lymphocytes or memory helper T lymphocytes in the circulation. We conclude that a moderate level GLA or EPA but not of other (n-6) or (n-3) PUFA can decrease lymphocyte proliferation but not production of interleukin-2 or interferon-gamma.     

Effects of chromium and copper depletion on lymphocyte reactivity to mitogens in diabetes-prone BHE/cdb rats

OBJECTIVE: The purpose of this study was to measure effects of chromium (Cr) and copper (Cu) depletion on lymphocyte reactivity to mitogens in diabetes-prone BHE/cdb rats. METHODS: A 2 x 2 factorial research design was used, and 40 BHE/cdb rats were fed with Cr- and/or Cu-depleted diets or adequate Cr and/or Cu diets for 21 wk. Cr and Cu concentrations in diets and mineral concentrations of tissues of BHE/cdb rats were measured by using flame and graphite furnace atomic absorption spectrometry. Three glucose tolerance tests were performed to monitor the development of diabetes or glucose intolerance at weeks 12, 18, and 21. Splenocytes (2 x 10(6)) were incubated with phytohemagglutinin-l (PHA-L), concanavalin A (ConA), and lipopolysaccharides (LPSs), respectively, for 72 h. Four hours before the end of the incubation, splenocytes were pulsed with 3H-thymidine. The 3H-thymidine uptake by lymphocytes was used to calculate a stimulation index. RESULTS: According to glucose tolerance tests, these rats did not develop diabetes or impaired glucose tolerance throughout the study. Average Cr concentrations were 0.98 to 1.03 mg Cr/kg of diet in adequate Cr diets and 8.2 to 14 micrograms Cr/kg of diet in Cr-depletion diets. Average Cu concentrations were 3.6 to 6.4 mg Cu/kg of diet in adequate Cu diets and 1.1 to 1.3 mg Cu/kg of diet in Cu-depletion diets. Organ weights did not differ significantly among treatment groups at the end of the study. Cr or Cu depletion significantly affected iron, zinc, and magnesium concentrations in the liver. A significant interactive effect of Cr and Cu was observed on lymphocyte proliferation with PHA-L stimulation at 25 micrograms/mL (P < 0.006). However, there were no significant effects of dietary treatment on lymphocyte proliferation with 10 micrograms/mL of PHA-L, ConA, or LPS stimulations. CONCLUSIONS: When Cr and Cu were adequate in the diets, there was an enhanced effect of Cu or Cr on lymphocyte proliferation. However, when Cr was depleted in the diet, there was a suppressive effect of Cu on lymphocyte proliferation. This result indicates that adequate amounts of Cr and Cu in the diet support the immune system.     

Toxicity of a soybean oil emulsion on human lymphocytes and neutrophils

BACKGROUND: The incorporation of lipid emulsions in parenteral diets is a requirement for energy and essential fatty acid supply to critically ill patients. In this study, the toxicity of a lipid emulsion rich (60%) in triacylglycerol of omega-6 polyunsaturated fatty acids on leukocytes from healthy volunteers was investigated. METHODS: Eleven volunteers were recruited, and blood samples were collected before infusion of a soybean oil emulsion, immediately afterwards, and 18 hours later. The cells were studied immediately after isolation and again after 24 hours or 48 hours in culture. The following determinations were made: composition and concentration of fatty acids in plasma, lymphocytes and neutrophils, lymphocyte proliferation, levels of cell viability, DNA fragmentation, phosphatidylserine externalization, mitochondrial depolarization, reactive oxygen species production, and neutral lipid accumulation. RESULTS: Soybean oil emulsion decreased lymphocyte proliferation and provoked neutrophil and lymphocyte apoptosis and necrosis. Evidence is presented herein that soybean oil emulsion is less toxic to neutrophils than to lymphocytes. The mechanism of cell death induced by this oil emulsion was characterized by mitochondrial membrane depolarization and neutral lipid accumulation but did not alter reactive oxygen species production. CONCLUSIONS: Soybean oil emulsion given as a single dose of 500 mL promotes lymphocyte and neutrophil death that may enhance the susceptibility of the patients to infections.     

Conjugated Linoleic Acid and Bone Biology

Osteoporosis, osteoarthritis and inflammatory joint disease afflict millions of people worldwide. Inflammatory cytokines inhibit chondrocyte proliferation and induce cartilage degradation for which part of the response is mediated by PGE₂. Excess production of PGE₂ is linked to osteoporosis and arthritis and is associated with bone and proteoglycan loss. PGE₂ also influences the IGF-I/IGFBP axis to facilitate bone and cartilage formation. Recent investigations with growing rats given butter fat and supplements of CLA demonstrated an increased rate of bone formation and reduced ex vivo bone PGE₂ production, respectively. Furthermore, the supplements of CLA isomers resulted in their enrichment in lipids of various bone compartments of animals. The effects of CLA on bone biology in rats (IGF action and cytokines) appear to be dependent on the level of n-6 and n-3 fatty acids in the diet; however, these studies generally showed that CLA decreased ex vivo bone PGE₂ production and in osteoblast-like cultures. Anti-inflammatory diets, including nutraceutical applications of CLA, may be beneficial in moderating cyclooygenase 2 (COX-2) activity or expression (influencing PGE₂ biosynthesis) and might help to reduce rheumatoid arthritis (secondary osteoporosis). This review summarizes findings of CLA on bone modeling in rats and effects on cellular functions of osteoblasts and chondrocytes. These experiments indicate that CLA isomers possess anti-inflammatory activity in bone by moderating prostanoid formation.     

Decreasing linoleic acid with constant alpha-linolenic acid in dietary fats increases (n-3) eicosapentaenoic acid in plasma phospholipids in healthy men

High linoleic acid (LA) intakes have been suggested to reduce alpha-linolenic acid [ALA, 18:3(n-3)] metabolism to eicosapentaenoic acid [EPA, 20:5(n-3)] and docosahexaenoic acid [DHA, 22:6(n-3)], and favor high arachidonic acid [ARA, 20:4(n-6)]. We used a randomized cross-over study with men (n = 22) to compare the effect of replacing vegetable oils high in LA with oils low in LA in foods, while maintaining constant ALA, for 4 wk each, on plasma (n-3) fatty acids. Nonvegetable sources of fat, except fish and seafoods, were unrestricted. We determined plasma phospholipid fatty acids at wk 0, 2, 4, 6, and 8, and triglycerides, cholesterol, serum CRP, and IL-6, and platelet aggregation at wk 0, 4, and 8. LA and ALA intakes were 3.8 +/- 0.12% and 1.0 +/- 0.05%, and 10.5 +/- 0.53% and 1.1 +/- 0.06% energy with LA:ALA ratios of 4:0 and 10:1 during the low and high LA diets, respectively. The plasma phospholipid LA was higher and EPA was lower during the high than during the low LA diet period (P < 0.001), but DHA declined over the 8-wk period (r = -0.425, P < 0.001). The plasma phospholipid ARA:EPA ratios were (mean +/- SEM) 20.7 +/- 1.52 and 12.9 +/- 1.01 after 4 wk consuming the high or low LA diets, respectively (P < 0.001); LA was inversely associated with EPA (r = -0.729, P < 0.001) but positively associated with ARA:EPA (r = 0.432, P < 0.001). LA intake did not influence ALA, ARA, DPA, DHA, or total, LDL or HDL cholesterol, CRP or IL-6, or platelet aggregation. In conclusion, high LA intakes decrease plasma phospholipid EPA and increase the ARA:EPA ratio, but do not favor higher ARA.     

Alterations in the surface-related phenomena of alveolar macrophages following inhalation of crocidolite asbestos and quartz dusts: an overview.

The possibility that immunological factors could be involved in the pathogenesis of asbestosis and silicosis was investigated. This study formed the basis of a Ph.D. Thesis. A brief discussion of the results obtained with particular reference to the differing effect of quartz and asbestos inhalation is presented. Rats were used as experimental animals and were exposed to the relevant dusts by inhalation to provide a model of the in vivo participation of the constituent mononuclear phagocytes. Early changes included alteration of surface morphology of the macrophages and an increased number of IgG receptor sites. In vivo membrane deposition of complement components on asbestos macrophages from crocidolite-dusted rats was demonstrated. When macrophages from crocidolite-dusted rats were cultured in vitro with splenic lymphocytes a prolonged physical interaction occurred followed by lymphocyte proliferation. The surface-related alterations leading to these phenomena were characterized. It is postulated that dusted macrophages participate in both cell-mediated and humoral interactions, and that host factors contribute to the development of dust diseases.     

Relationship between the fatty acid composition of rat lymphocytes and immune functions

The effects of dietary lipids on the fatty acid composition, activation and proliferation of lymphocytes were investigated. Weanling male Wistar rats were fed for 8 weeks on one of two low-fat diets which contained 50 g lipid/kg, or one of two high-fat diets containing 200 g lipid/kg, from either coconut oil or soyabean oil. The fatty acid composition of phospholipids from splenocyte membranes was affected by dietary lipid manipulation, and these differences influenced lymphocyte functions. Increased levels of linoleic acid in spleen lymphocytes correlated negatively with interleukin-2 receptor alpha-chain expression determined either by measuring the mean fluorescence or by the proportion of cells staining positive for CD25, and with the cell proliferation index. However, we found a positive correlation between interleukin-2 receptor alpha-chain expression determined by measuring the mean fluorescence and the cell proliferation index with the oleic acid concentration of spleen lymphocytes. Since phospholipid hydrolysis occurs early in lymphocyte activation, immunosuppressive effects induced by polyunsaturated fatty acids, described in the literature, could be due to an increase of linoleic acid or a decrease of oleic acid affecting many components of plasma-membrane-associated events involved in lymphocyte activation.     

Limited effect of eicosapentaenoic acid on T-lymphocyte and natural killer cell numbers and functions in healthy young males

OBJECTIVE: Greatly increasing the amount of long-chain omega-3 polyunsaturated fatty acids in the diet has been reported in some studies to decrease T-lymphocyte and natural killer functions. However, dose-response relations have not been identified. The objective of this study was to determine the effect of supplementing the diet of young male subjects with different amounts of an oil rich in eicosapentaenoic acid (EPA) on T-lymphocyte proliferation, cytokine production by T lymphocytes, and natural killer cell activity. METHODS: In a placebo-controlled, double-blind, parallel study, healthy young (18 to 42 y) males were randomized to one of four supplements. These were placebo (no additional omega-3 polyunsaturated fatty acids) or different amounts of an EPA-rich oil that provided 1.35, 2.7, or 4.05 g/d of EPA for 12 wk. Blood samples were taken at baseline and after 12 wk. RESULTS: Eicosapentaenoic acid was incorporated in a linear dose-response fashion into mononuclear cell phospholipids. EPA did not alter the proportions of T lymphocytes, helper T lymphocytes, cytotoxic T lymphocytes, B lymphocytes, or natural killer cells in the bloodstream. T-lymphocyte proliferation in response to concanavalin A and the production of the cytokines interleukin-2, interferon-gamma, and interleukin-10 were not affected by the different treatments. However, interleukin-4 production was increased with increasing intake of EPA. Natural killer cell activity was little affected by the treatments, although there was a trend for EPA to increase activity at a low effector-to-target cell ratio. CONCLUSION: T-lymphocyte and natural killer cell numbers and function in healthy young males are little affected by supplemental EPA intakes up to 4 g/d.     

(n-3) PUFA alter raft lipid composition and decrease epidermal growth factor receptor levels in lipid rafts of human breast cancer cells

To determine the mechanism by which the (n-3) fatty acids (FA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) decrease proliferation and induce apoptosis in MDA-MB-231 human breast cancer cells, we examined the effects of EPA and DHA on the lipid composition of lipid rafts as well as epidermal growth factor receptor (EGFR) raft localization and phosphorylation. (n-3) FA (a combination of EPA and DHA) inhibited (P < 0.05) the growth of MDA-MB-231 cells by 48-62% in the presence and absence, respectively, of linoleic acid (LA). More EPA and DHA were incorporated into lipid rafts isolated from MDA-MB-231 cells after treatment with (n-3) FA compared with cells treated with LA (P < 0.05). EPA and DHA treatment decreased (P < 0.05) lipid raft sphingomyelin, cholesterol, and diacylglycerol content and, in the absence of LA, EPA and DHA increased (P < 0.05) raft ceramide levels. Furthermore, there was a marked decrease in EGFR levels in lipid rafts, accompanied by increases in the phosphorylation of both EGFR and p38 mitogen-activated protein kinase (MAPK), in EPA+DHA-treated cells (P < 0.05). As sustained activation of the EGFR and p38 MAPK has been associated with apoptosis in human breast cancer cells, our results indicate that (n-3) FA modify the lipid composition of membrane rafts and alter EGFR signaling in a way that decreases the growth of breast tumors.     

Dose-dependent activation of immune function in mice by ingestion of Maharishi Amrit Kalash 5

This study was carried out to evaluate the dose-effects of ingestion of Maharishi Amrit Kalash 5 (MAK 5), an Ayurvedic food supplement, on the immune function in 10 week female inbred BALB/c mice. Superoxide anion (O₂ ) production of peritoneal macrophages and the response of spleen cells to concanavalin A (Con A) were examined in mice given MAK 5 by gastric intubation of an aqueous emulsion at the doses of 10, 50, 100 and 200 mg/kg once a day for 20 days. Glucose consumption of peritoneal macrophages in the MAK 5-treated mice at all doses after 24 hours of incubation, and only at the dose of 200 mg/kg after 48 hours of incubation were significantly higher than those in the control group. O₂ production of peritoneal macrophages in the presence of stimulator was significantly higher in the MAK 5-treated group at the dose of 200 mg/kg than in the control group. Activities of β -glucuronidase and lactate dehydrogenase in the peritoneal macrophages were significantly increased in the MAK 5treated mice at all doses. MAK 5 did not enhance spontaneous splenic lymphocyte proliferation at any dose in mice. Stimulation indices in the MAK 5-treated groups at the doses of 50, 100 and 200 mg/kg were significantly higher than that of the control group. These results indicate that gastric intubation of MAK 5 once a day at the dose of 50 mg/kg enhances not only macrophage function but also lymphocyte responsiveness in mice.