PubMed Health⌕ Search

Biomedical subjects

P C Calder

Publications and source records attributed to P C Calder.

At least 91 records · Page 5Linked to original sources
PubMed1997

Effects of variations in the proportions of saturated, monounsaturated and polyunsaturated fatty acids in the rat diet on spleen lymphocyte functions.

To obtain further information about the immunomodulatory effects of specific dietary fatty acids, weanling male rats were fed for 6 weeks on high-fat (178 g/kg) diets which differed according to the principal fatty acids present. The nine diets used differed in their contents of palmitic, oleic, linoleic and alpha-linolenic acids; as a result the total polyunsaturated fatty acid (PUFA) content and the PUFA:saturated fatty acid ratio varied (from 17.8 to 58.5 g/100 g fatty acids and from 0.28 to 5.56 respectively). The n-6 PUFA:n-3 PUFA ratio was kept constant in all diets at approximately 7.0. The fatty acid composition of the serum and of spleen lymphocytes were significantly influenced by that of the diet fed. The ex vivo proliferation of spleen lymphocytes decreased as the level of oleic acid in the diet increased. Spleen natural killer cell activity decreased as the oleic acid content of the diet increased and increased as the palmitic acid content of the diet increased. The extent of the effects of these fatty acids on lymphocyte functions was modified by the nature of the background fatty acid composition of the diet.

Animals↗
PubMed1997

n-3 polyunsaturated fatty acids and cytokine production in health and disease.

Arachidonic-acid-derived eicosanoids modulate the production of pro-inflammatory and immunoregulatory cytokines. Overproduction of these cytokines is associated with both septic shock and chronic inflammatory diseases. The n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid, which are found in fish oils, suppress the production of arachidonic-acid-derived eicosanoids and EPA is a substrate for the synthesis of an alternative family of eicosanoids. Thus, dietary fats which are rich in n-3 PUFAs have the potential to alter cytokine production. Animal studies have provided a great deal of evidence that feeding plant or fish oils rich in n-3 PUFAs does alter the ex vivo production of tumour necrosis factor (TNF), interleukin 1 (IL-1), IL-6 and IL-2, but many contradictory observations have been made; it is most likely that the discrepancies in the literature result from differences in the cell types and experimental protocols used. Human studies provide more consistent data: several studies have shown that supplementation of the diet of healthy volunteers results in reduced ex vivo production of IL-1, IL-6, TNF and IL-2 by peripheral blood mononuclear cells. Similar findings have been made in patients with rheumatoid arthritis and multiple sclerosis. Animal studies indicate that dietary fish oil reduces the response to endotoxin and to pro-inflammatory cytokines, resulting in increased survival; such diets have been beneficial in some models of bacterial challenge, chronic inflammation and auto-immunity. These beneficial effects of dietary n-3 PUFAs may be of use as a therapy for acute and chronic inflammation and for disorders which involve an inappropriately activated immune response.

Animals↗
PubMed1996

Inhibition of ICE-family cysteine proteases rescues murine lymphocytes from lipoxygenase inhibitor-induced apoptosis.

Two lipophilic derivatives of caffeic acid which inhibit lipoxygenase, caffeic acid phenethyl ester (CAPE) and N,N'-dicyclohexyl-O-(3,4-dihydroxycinnamoyl)-isourea (DCHCU), reduced the proliferative response of murine splenocytes to concanavalin A in vitro. Both CAPE and DCHCU induced apoptosis in murine thymocyte cultures as verified by flow cytometry and by visualisation of DNA with acridine orange staining. CAPE-induced apoptosis was inhibited by z-VAD-fmk, an inhibitor of the interleukin-1beta-converting enzyme family of cysteine proteases. We suggest that the lipoxygenase pathway of arachidonic acid metabolism plays a role in regulating lymphocyte responses such as proliferation and apoptosis.

Amino Acid Chloromethyl Ketones↗
PubMed1996

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

Previous studies have reported that feeding rats diets rich in fish oils, which contain high proportions of the n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic and docosahexaenoic acids, results in lowering of blood lipid levels and suppression of lymphocyte functions tested ex vivo and in vivo. The effects of other n-3 PUFA, such as alpha-linolenic acid, which is found in high proportions in linseed oil, are not as well documented. Therefore, in the present study, weanling male rats were fed for six weeks on one of five high-fat (20% by weight) diets made by mixing together sunflower and linseed oils; the resulting blends had n-6/n-3 PUFA ratios of 112.5:1 (pure sunflower oil), 14.8:1, 6.5:1, 0.81:1, and 0.33:1 (pure linseed oil); the levels of all other components in the diet were identical. The final body weight and total dissectable fat were lowest in rats fed the pure linseed oil diet. Serum cholesterol, triacylglycerol and nonesterified fatty acid concentrations decreased as the n-6/n-3 PUFA ratio of the diet decreased. The fatty acid composition of the serum and of spleen lymphocytes was influenced by the diet fed-there was a progressive decrease in the proportions of linoleic and arachidonic acids and a progressive increase in the proportion of alpha-linolenic acid as the n-6/n-3 PUFA ratio of the diet decreased. Eicosapentaenoic and docosahexaenoic acids were detected in the serum but not in spleen lymphocytes. Inclusion of alpha-linolenic acid in the diet resulted in significant suppression of spleen lymphocyte proliferation in response to the T-cell mitogen concanavalin A and in spleen lymphocyte natural killer cell activity, both measured ex vivo. The localized graft vs. host response, a measure of cell-mediated immunity in vivo, progressively decreased as the n-6/n-3 PUFA ratio of the diet decreased. Thus, this study shows that dietary alpha-linolenic acid results in lowered blood lipid levels and suppressed lymphocyte functions ex vivo and in vivo. With respect to these effects, alpha-linolenic acid is as potent as dietary fish oil.

Animal Feed↗
PubMed1996

The effect of propolis and its components on eicosanoid production during the inflammatory response.

To investigate the possible mechanism of the therapeutic action of propolis, we studied: (a) the effect of propolis, its components, caffeic acid phenethyl ester (CAPE), caffeic acid (CA), quercetin and naringenin, as well as the synthetic compounds indomethacin (IM) and nordihydroguaiaretic acid (NDGA), and a novel lipoxygenase inhibitor N,N'-dicyclohexyl-O-(3,4-dihydroxycinnamoyl)isourea (DCHCU) on eicosanoid production by mouse peritoneal macrophages in vitro; (b) the effect of IM, NDGA, CA, CAPE, DCHCU and propolis on eicosanoid production during acute inflammation in vivo; and (c) the ex vivo and in vivo effect of dietary propolis on arachidonic acid metabolism. The ethanol extract of propolis suppressed prostaglandin and leukotriene generation by murine peritoneal macrophages in vitro and during zymosan-induced acute peritoneal inflammation in vivo. Dietary propolis significantly suppressed the lipoxygenase pathway of arachidonic acid metabolism during inflammation in vivo. CAPE was the most potent modulator of the arachidonic acid cascade among the propolis components examined.

Animals↗
PubMed1996

The effects of olive oil upon rat serum lipid levels and lymphocyte functions appear to be due to oleic acid.

In order to investigate whether previously reported effects of feeding olive oil (OO) upon rat serum lipid concentrations and immune cell functions are due to oleic acid, weanling rats were fed for 6 weeks on diets containing 20% by weight of OO, safflower oil (SO), or high oleic acid sunflower oil (HOSO); a low-fat (LF) diet containing 2.5% by weight of lipid was used as a control. Feeding the OO or HOSO diets resulted in an elevated serum triacylglycerol concentration as compared with feeding the LF or SO diets. The serum total cholesterol concentrations were raised in the animals fed the high-fat diets and were highest in animals fed the OO or the HOSO diet. The fatty acid composition of the serum and of spleen lymphocytes reflected that of the diet fed. The mitogen-stimulated spleen lymphocyte proliferation ex vivo was significantly lower following OO or HOSO feeding as compared with LF or SO feeding. Similarly, feeding the OO or the HOSO diet resulted in lower spleen natural killer cell activity as compared with LF or SO feeding. These observations indicate that the effects of OO feeding are most likely due to oleic acid rather than to other components of OO.

Animals↗
PubMed1995

Influence of cell culture conditions on diet-induced changes in lymphocyte fatty acid composition.

The effect of a range of dietary lipids on the fatty acid composition and membrane fluidity of lymphocytes was investigated. The effects of subsequent culture of these lymphocytes in medium containing autologous serum, foetal calf serum or a serum-free supplement were assessed; this was considered important, since many studies investigating the effects of dietary lipid manipulation on immune function have used protocols involving a variety of cell culture conditions when performing tests of immune function. Weanling Lewis rats were fed for 10 weeks on a low-fat (LF; 20 g/kg) diet or on high fat diets containing 200 g/kg of either hydrogenated coconut oil (HCO), olive oil (OO), safflower oil (SO), evening primrose oil (EPO) or menhaden oil (MO). The fatty acid composition of the phospholipid fractions of lymphocytes from the spleen was altered by dietary lipid manipulation, whereas the fatty acid composition of thymic lymphocytes was not modified significantly. In general, the changes in the fatty acid composition of spleen lymphocytes reflected the fatty acid composition of the diets themselves. Despite the considerable changes in the fatty acid composition of lymphocytes from spleen, dietary lipid manipulation had no effect on the plasma membrane fluidity of these cells. Culturing lymphocytes in autologous serum allowed some, but not all, of the diet-induced changes in fatty acid composition to be maintained. The effects of dietary lipid manipulation were totally reversed when lymphocytes were cultured in FCS. Culturing lymphocytes in serum-free medium not only reversed any effects of dietary manipulation, but also markedly increased the appearance of palmitoleic and oleic acids, at the expense of palmitic and stearic acids, suggesting activation of the delta 9 desaturase when these cells were cultured in the absence of exogenous lipid. This study suggests that cell culture conditions have significant influence on the changes in lymphocyte fatty acid composition brought about by dietary lipid manipulation and may therefore influence the outcome of functional tests.

Animals↗
PubMed1995

Effects of dietary lipid manipulation upon graft vs host and host vs graft responses in the rat.

The popliteal lymph node (PLN) assay was used to establish whether dietary lipids with differing fatty acid compositions could affect cell-mediated immunity in the rat. Weanling rats were fed for 4 weeks on a lowfat (2.5% by weight; LF) diet or on diets containing 20% (by weight) hydrogenated coconut oil (HCO), olive oil (OO), safflower oil (SO), evening primrose oil (EPO), or menhaden (fish) oil (MO). Feeding the MO diet suppressed the graft vs host response compared with feeding the LF, HCO, SO, or EPO diets, while feeding the OO diet suppressed this response compared with feeding the LF or EPO diets. Feeding the MO diet suppressed the host vs graft response compared with feeding each of the other diets. Following the graft vs host reaction, PLN lymphocytes from animals fed the MO diet had significantly lower levels of expression of LFA-1 and CD2 compared with PLN lymphocytes from animals fed the LF diet; furthermore, they had lower levels of expression of T-cell receptor (TcR), CD4, CD8, LFA-1, and CD2 compared with lymphocytes from animals fed some, and in the case of CD2 each, of the other high-fat diets. Feeding the MO diet resulted in a lower proportion of cells expressing the interleukin-2 receptor, indicating an inhibition of lymphocyte activation, and a lower proportion of CD16+/CD3- cells, indicating a decrease in the proportion of NK cells within the PLN. Following the host vs graft reaction, PLN lymphocytes from animals fed the MO diet had significantly lower levels of expression of TcR and CD8 compared with lymphocytes from animals fed each of the other diets; furthermore, they had lower levels of expression of CD4, CD2, and LFA-1 compared with lymphocytes from animals fed the LF, HCO, OO, or SO diets. These observations indicate that the smaller PLN size of animals fed the MO diet results from an inhibition of activation and subsequent proliferation of cells within the node and perhaps also a suppression of movement of cells from the bloodstream to the PLN, due to decreased level of expression of adhesion molecules. These lowered levels of expression might be due to an inhibitory effect of the n-3 polyunsaturated fatty acids found in MO upon components of the signal transduction pathways involved in lymphocyte activation or upon expression of the genes for the surface molecules or both.

Animals↗
PubMed1995

The effects of dietary lipid manipulation on the production of murine T cell-derived cytokines.

Lymphocytes play an important part in the development and progression of a number of autoimmune and inflammatory disorders, which are characterized by the presence of activated T cells and cytokines at the site of tissue injury and in the circulation. There has been considerable interest in using dietary polyunsaturated fatty acids (PUFA), particularly the n-3 PUFA found in fish oils, in the therapy of these conditions; such therapies aim, primarily, to suppress T-lymphocyte activity. While several studies have investigated the effects of fatty acids on the production of monocyte- and macrophage-derived cytokines, few have investigated their effects on the production of T cell-derived cytokines. Each of these studies have been restricted to IL-2 and have produced results which are not entirely clear. Moreover, there have been no studies to investigate the effects of dietary lipids other than fish oils on IL-2 production or the effects of dietary lipids on lymphokines other than IL-2. To investigate the effects of dietary lipid manipulation on the production of IL-2, IL-4, IL-10 and IFN-gamma by lymphocytes, mice were fed for 8 weeks on a low fat (LF) diet or one of 4 high fat diets, which contained 20% (by weight) hydrogenated coconut oil (HCO), olive oil (OO), safflower oil (SO) or menhaden oil (MO). Culture medium of lymphocytes from mice fed the OO or SO diets contained significantly more IL-2 than that of lymphocytes from mice fed the LF or HCO diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗