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Biomedical subjects

P C Calder

Publications and source records attributed to P C Calder.

At least 73 records · Page 4Linked to original sources
PubMed1998

Low levels of eicosapentaenoic and docosahexaenoic acids mimic the effects of fish oil upon rat lymphocytes.

Fish oil is rich in the long chain n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); typically these fatty acids constitute 20 to 25 g/100 g total fatty acids in fish oil. Feeding rodents diets rich in fish oil has been shown to decrease lymphocyte proliferation and natural killer cell activity. It is not known what level of EPA + DHA is required in the diet to exert these effects. This question was addressed in the current study. Weanling rats were fed on high fat (178 g/kg) diets which contained 4.4 g alpha-linolenic acid (control) or 4.4 g EPA + DHA (4.4 EPA + DHA) or 6.6 g EPA + DHA (6.6 EPA + DHA)/100 g total fatty acids. The n-6 to n-3 polyunsaturated fatty acid ratio was maintained at approximately 7. The fatty acid compositions of the serum and of spleen leukocytes were markedly influenced by that of the diet. Spleen lymphocyte proliferation in response to concanavalin A, spleen natural killer cell activity and PGE2 production by spleen leukocytes were reduced by feeding the EPA + DHA diets compared with feeding the control diet; the 4.4 and 6.6 EPA + DHA diets caused very similar reductions. The 4.4 EPA + DHA diet reduced popliteal lymph node weight following a localised graft versus host response; this response was not investigated in rats fed the 6.6 EPA + DHA diet. The reductions in lymphocyte functions and in the in vivo graft versus host response caused by the EPA + DHA diets were similar to those previously reported following the feeding of diets rich in fish oil. Thus, this study shows that diets containing relatively low levels of EPA + DHA (20 to 25% of the level found in fish oil) exert immunomodulatory effects. Furthermore, this study suggests that the maximal effect of EPA + DHA is exerted when these fatty acids constitute a level of less than or equal to 4.4 g/100 g total dietary fatty acids.

Animals↗
PubMed1998

Dietary fish oil suppresses human colon tumour growth in athymic mice.

1. Human colon tumour growth, initiated by subcutaneous inoculation of HT29 cells, was measured in athymic mice fed ad libitum on high-fat (210 g/kg) diets rich in coconut oil (CO), olive oil (OO), safflower oil (SO) or fish oil (FO); a low fat (LF; 25 g/kg) diet was used as the control. In one experiment the mice were fed the experimental diets for 3 weeks before HT29 cell inoculation and were killed 2 weeks post-inoculation. In a second experiment the mice were maintained on the LF diet until 4 days post-HT29 cell inoculation; they were then fed the experimental diets for 17 days. 2. Compared with mice fed the LF diet, tumour size was increased in mice fed the CO, OO or SO diets for 3 weeks before HT29 cell inoculation; FO feeding did not significantly increase tumour size. 3. Feeding mice the CO or OO diets from 4 days post-inoculation increased tumour growth rate and tumour size compared with feeding the LF, SO or FO diets; tumour growth rate and size did not differ among mice fed the latter diets. 4. The fatty acid composition of the tumours was markedly influenced by the fatty acid composition of the diet. 5. We conclude that human colon tumour growth is influenced by the type of fat consumed in the diet. Human colon tumour growth in this model is promoted by feeding high fat diets rich in medium chain saturated fatty acids (CO) or monounsaturated fatty acids (OO). A high fat diet, rich in long chain n - 3 polyunsaturated fatty acids (FO), does not promote colon tumour growth. The effect of a high fat diet rich in n - 6 polyunsaturated fatty acids (SO) depends upon the time at which it is fed: if fed before tumour cell inoculation such a diet promotes tumour growth, whereas if fed once tumour growth is initiated it does not. This suggests that n - 6 polyunsaturated fatty acids promote the initiation of colon tumour growth, but do not exert growth-promoting effects on colon tumours once they are established.

Adipose Tissue↗
PubMed1998

Dietary fish oil diminishes lymphocyte adhesion to macrophage and endothelial cell monolayers.

To further investigate the immunomodulatory effects of dietary lipids, rats were fed on a low-fat diet or on high-fat diets that contained hydrogenated coconut, olive, safflower, evening primrose or fish oil as the principal fat source. The fish oil diet decreased the level of expression of CD2, CD11a, CD18 and CD44 on the surface of freshly prepared lymphocytes and of CD2, CD11a, CD18, CD54 (intercellular adhesion molecule-1; ICAM-1) and CD62L (L-selectin) on the surface of concanavalin A (Con A)-stimulated lymphocytes. The olive oil diet also resulted in decreased expression of some adhesion molecules. The fish or olive oil diets, and to a lesser extent the safflower or evening primrose oil diets, decreased the adhesion of both freshly prepared and Con A-stimulated lymphocytes to macrophage monolayers. The fish oil diet, and to a lesser extent the olive or evening primrose oil diets, reduced the ability of Con A-stimulated lymphocytes to adhere to untreated endothelial cells. Furthermore, the fish oil diet resulted in a 50% reduction in Con A-stimulated lymphocyte adhesion to tumour necrosis factor-alpha (TNF-alpha)-stimulated endothelial cells. This study demonstrates that dietary lipids affect the expression of functionally important adhesion molecules on the surface of lymphocytes. Furthermore, this study suggests that such diet-induced effects on adhesion molecule expression might alter the ability of lymphocytes to bind to macrophages and to endothelial cells. Of the diets studied fish oil causes the most significant effects. The results of this study suggest that a reduction in cellular infiltration may partly explain the protective effect of a fish-oil-rich diet against the development of inflammatory and cardiovascular diseases.

Animals↗
PubMed1998

Effect of olive oil on immune function in middle-aged men.

Consumption of diets rich in monounsaturated fatty acids (MUFAs) has been linked with a low prevalence of atherosclerosis and there has been great interest in the effects of MUFAs on lipoprotein metabolism. Less attention has been paid to the effects of MUFAs on the immune system, yet cells of the immune system are an inherent part of the inflammatory events involved in atherosclerosis and several animal studies showed that olive oil has some potent immunomodulatory actions. We therefore considered it important to investigate the effects of chronic consumption of MUFAs on several immune cell functions in healthy humans. Healthy middle-aged males entered a double-blind, randomized, controlled trial in which they consumed either a MUFA diet or a control diet for 2 mo. There was a significant decrease in the expression of intercellular adhesion molecule 1 by peripheral blood mononuclear cells from subjects consuming the MUFA diet. Consumption of the MUFA diet did not affect natural killer cell activity or proliferation of mitogen-stimulated leukocytes. The effects of a MUFA-rich diet on adhesion molecule expression may have implications for the influence of dietary fat on inflammatory diseases, including atherosclerosis.

Adult↗
PubMed1998

Immunoregulatory and anti-inflammatory effects of n-3 polyunsaturated fatty acids.

1. Fish oils are rich in the long-chain n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acids. Linseed oil and green plant tissues are rich in the precursor fatty acid, alpha-linolenic acid (18:3n-3). Most vegetable oils are rich in the n-6 PUFA linoleic acid (18:2n-6), the precursor of arachidonic acid (20:4n-6). 2. Arachidonic acid-derived eicosanoids such as prostaglandin E2 are pro-inflammatory and regulate the functions of cells of the immune system. Consumption of fish oils leads to replacement of arachidonic acid in cell membranes by eicosapentaenoic acid. This changes the amount and alters the balance of eicosanoids produced. 3. Consumption of fish oils diminishes lymphocyte proliferation, T-cell-mediated cytotoxicity, natural killer cell activity, macrophage-mediated cytotoxicity, monocyte and neutrophil chemotaxis, major histocompatibility class II expression and antigen presentation, production of pro-inflammatory cytokines (interleukins 1 and 6, tumour necrosis factor) and adhesion molecule expression. 4. Feeding laboratory animals fish oil reduces acute and chronic inflammatory responses, improves survival to endotoxin and in models of autoimmunity and prolongs the survival of grafted organs. 5. Feeding fish oil reduces cell-mediated immune responses. 6. Fish oil supplementation may be clinically useful in acute and chronic inflammatory conditions and following transplantation. 7. n-3 PUFAs may exert their effects by modulating signal transduction and/or gene expression within inflammatory and immune cells.

Animals↗
PubMed1997

Effects of varying the type of saturated fatty acid in the rat diet upon serum lipid levels and spleen lymphocyte functions.

To obtain further information about the effects of specific dietary saturated fatty acids, weanling male rats were fed for 6 weeks on low fat (7.7% by weight) or high fat (17.8% by weight) diets which differed according to the principal fatty acids present. The diets were rich in caprylic and capric acids (medium chain triacylglycerols; MCT), lauric acid, palmitic acid at the sn-1(3) position, palmitic acid at the sn-2 position or stearic acid. The total proportions of saturated (42-46%), monounsaturated (36%), n-6 polyunsaturated (15%) and n-3 polyunsaturated (2.2%) fatty acids were the same in all diets. Serum cholesterol concentrations were not different among rats fed the different diets, except that the concentration in the serum of rats fed the high fat diet with palmitic acid in the sn-2 position was high. This was reflected in higher HDL and LDL cholesterol concentrations in the serum of animals fed this diet. Triacylglycerol (TAG) concentrations tended to be higher in the serum of rats fed the low fat diets compared with those fed the high fat diets. They were lowest in the serum of MCT-fed rats irrespective of the level of fat in the diet and were highest in the serum of rats fed the low fat diet rich in stearic acid. These differences were due to lower chylomicron and VLDL TAG concentrations in the serum of MCT-fed rats and higher chylomicron and VLDL TAG concentrations in the serum of low fat, stearic acid-fed animals. The fatty acid compositions of the serum and of spleen lymphocytes were influenced by that of the diet fed. The ex vivo proliferation of lymphocytes from the spleens of rats fed the high fat diet rich in palmitic acid at the sn-2 position was greater than that of lymphocytes from animals fed the other diets. Natural killer (NK) cell activity tended to be lower for spleen lymphocytes from rats fed high fat diets than for those fed low fat diets irrespective of the principal saturated fatty acid present. NK cell activity was highest for spleen lymphocytes from animals fed the diets rich in palmitic acid and was lowest for those from animals fed the high fat diet rich in stearic acid. Spleen lymphocytes from the latter animals had the lowest proportion of CD16+ cells, a marker for NK cells. Thus, this study shows that the type of saturated fatty acid present in the diet not only has subtle effects upon blood lipid and lipoprotein levels but can significantly affect lymphocyte functions. Spleen lymphocyte NK cell activity is decreased as the fat content of the diet increases. NK cell number and activity are reduced by a high fat diet rich in stearic acid. Spleen lymphocyte proliferation is enhanced by palmitic acid-rich diets, particularly if palmitic acid is in the sn-2 position of dietary TAG.

Animals↗
PubMed1997

Dietary fish oil diminishes the antigen presentation activity of rat dendritic cells.

Rats were fed for 6 weeks on a low fat (LF) diet or on high fat diets containing safflower oil [SO; rich in n-6 polyunsaturated fatty acids (PUFAs)] or fish oil (FO; rich in n-3 PUFAs). Lymph-borne dendritic cells (L-DC) were isolated after cannulation of the thoracic duct and were used as antigen [keyhole limpet hemocyanin (KLH)]-presenting cells in an ex vivo assay that used KLH-sensitized spleen lymphocytes as the responder cells. FO feeding significantly diminished the antigen presentation activity of L-DC compared with L-DC from rats fed each of the other diets. The antigen presentation activity of L-DC from rats fed the SO diet was greater than that of L-DC from rats fed the LF diet. Feeding the FO diet significantly reduced both the proportion of CD2-positive L-DC and the level of CD2 expression on L-DC compared with feeding each of the other diets; the proportions of L-DC staining positive for CD40, CD18, CD54, CD11a, and MHC II were unaffected by diet. However, FO feeding reduced the level of expression of CD18, CD11a, MHC II, and CD54 on L-DC compared with feeding the other two diets; the level of expression of CD40 was unaffected by diet. This is the first study to report effects of dietary fatty acids on dendritic cells. The suppressive effect of FO feeding may account for some of the beneficial effects of n-3 polyunsaturated fatty acids observed in clinical settings, such as prolonged survival of grafts and diminished chronic inflammatory responses. However, such an effect may also be detrimental because host defense toward bacterial and other antigens could be compromised.

Animals↗
PubMed1997

Fatty acid composition of lymphocytes and macrophages from rats fed fiber-rich diets: a comparison between oat bran- and wheat bran-enriched diets.

The effect of oat bran- (OBD) and wheat bran-enriched diets (WBD) on fatty acid composition of neutral lipids and phospholipids of rat lymphocytes and macrophages was investigated. In neutral lipids of lymphocytes, OBD reduced the proportion of palmitoleic acid (48%), whereas WBD reduced by 43% palmitoleic acid and raised oleic (18%), linoleic (52%), and arachidonic (2.5-fold) acids. In neutral lipids of macrophages, OBD increased palmitic (16%) and linoleic (29%) acids and slightly decreased oleic acid (15%). The effect of WBD, however, was more pronounced: It reduced myristic (60%), stearic (24%) and arachidonic (63%) acids, and it raised palmitic (30%) and linoleic (2.3-fold) acids. Neither OBD nor WBD modified the composition of fatty acids in phospholipids of lymphocytes. In contrast, both diets had a marked effect on composition of fatty acids in macrophage phospholipids. OBD raised the proportion of myristic (42%) and linoleic (2.4-fold) acids and decreased that of lauric (31%), palmitoleic (43%), and arachidonic (29%) acids. WBD increased palmitic (18%) and stearic (23%) acids and lowered palmitoleic (35%) and arachidonic (78%) acids. Of both cells, macrophages were more responsive to the effect of the fiber-rich diets on fatty acid composition of phospholipids. The high turnover of fatty acids in macrophage membranes may explain the differences between both cells. The modifications observed due to the effects of both diets were similar in few cases: an increase in palmitic and linoleic acids of total neutral lipids occurred and a decrease in palmitoleic and arachidonic acids of phospholipid. Therefore, the mechanism involved in the effect of both diets might be different.

Animals↗
PubMed1997

N-3 polyunsaturated fatty acids and immune cell function.

The amount and type of eicosanoids made can be affected by the type of fat consumed in the diet. It is now apparent that both eicosanoids and n-3 PUFAs are potent modulators of lymphocyte and M phi functions in vitro. Inclusion in the diet of high levels of certain lipids containing n-3 PUFAs markedly affects the functions of cells of the immune system subsequently tested in vitro. Cellular components of both natural and acquired immunity are affected. In vivo tests are perhaps the most appropriate approach for determining the effect of different dietary n-3 PUFAs upon immune function. Several studies indicate that diets rich in n-3 PUFAs are anti-inflammatory and immunosuppressive in vivo, although there have been relatively few studies in man. Although some of the effects of n-3 PUFAs may be brought about by modulation of the amount and types of eicosanoids made, it is clear that these fatty acids can also elicit their effects by eicosanoid-independent mechanisms (Fig. 12). Such n-3 PUFA-induced effects may be of use as a therapy for acute and chronic inflammation, for disorders which involve an inappropriately-activated immune response and for the enhancement of graft survival.

Animals↗
PubMed1997

Antimicrobial action of propolis and some of its components: the effects on growth, membrane potential and motility of bacteria.

The effect of the natural bee product propolis on the physiology of microorganisms was investigated using B. subtilis, E. coli and R. sphaeroides. An ethanolic extract of propolis had a bactericidal effect caused by the presence of very active, but labile, ingredients. The exact bactericidal effect of propolis was species dependent: it was effective against gram-positive and some gram-negative bacteria. Propolis and some of its cinnamic and flavonoid components were found to uncouple the energy transducing cytoplasmic membrane and to inhibit bacterial motility. These effects on the bioenergetic status of the membrane may contribute to the antimicrobial action of propolis and its observed synergism with selected antibiotics.

Anti-Bacterial Agents↗
PubMed1997

Level of polyunsaturated fatty acids and the n-6 to n-3 polyunsaturated fatty acid ratio in the rat diet alter serum lipid levels and lymphocyte functions.

In order to further examine the effects of dietary polyunsaturated fatty acids (PUFA) upon blood lipid levels and lymphocyte functions, weanling rats were fed for 6 weeks on high fat (178 g/kg) diets which differed in the ratio of n-6:n-3 PUFA (100, 20, 10, 5, 1) and in the absolute level of PUFA (17.5 or 35 g/100 g fatty acids). The n-6:n-3 PUFA ratio of the diets was decreased by replacing linoleic acid with alpha-linolenic acid while the PUFA content of the diets was decreased by replacing PUFA with palmitic acid. Serum cholesterol concentrations decreased as the n-6:n-3 PUFA ratio of the low PUFA diet decreased. The ex vivo proliferation of spleen lymphocytes from rats fed the low PUFA diets decreased as the n-6:n-3 PUFA ratio of the diet decreased; the proliferation of spleen lymphocytes from high PUFA-fed rats was less affected by the n-6:n-3 PUFA ratio of the diet. Natural killer cell activity was lower for spleen lymphocytes from rats fed high PUFA diets with n-6:n-3 PUFA ratios of 100 or 20 than for those from rats fed low PUFA diets with these ratios. The natural killer cell activity of spleen lymphocytes decreased as the n-6:n-3 PUFA ratio of the low PUFA diet decreased. These findings indicate that dietary alpha-linolenic acid has significant blood lipid-lowering and immunomodulatory effects in rats, but that the effect is dependent upon the total PUFA content of the diet. The ratios of linoleic and alpha-linolenic acids to other fatty acids (e.g. palmitic, oleic) are important in determining the precise effect of manipulations of the fatty acid composition of the diet.

Analysis of Variance↗