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Biomedical subjects

D Rotondo

Publications and source records attributed to D Rotondo.

At least 19 recordsLinked to original sources
PubMed2005

Effect of CLA supplementation on immune function in young healthy volunteers.

OBJECTIVES: This study investigated the effect of dietary CLA supplementation (3g/day; 50:50 mix of the two major isomers) on the immune system and plasma lipids and glucose of healthy human (male and female) volunteers. DESIGN: Double-blind, randomized, reference-controlled study. SUBJECT AND INTERVENTION: A total of 28 healthy male and female participants aged 25-50 y received either high oleic sunflower oil (reference) or 50% CLA 9-11 and 50% CLA 10-12 CLA isomers (50:50 CLA-triglyceride form). The treatments were given as supplements in soft-gel capsules providing a total 3 g (6 x 500 mg capsules) per day in treatment groups for 12 weeks. A 12-week washout period followed the intervention period. RESULTS: Levels of plasma IgA and IgM were increased (P < 0.05 and 0.01 respectively), while plasma IgE levels were decreased (P < 0.05). CLA supplementation also decreased the levels of the proinflammatory cytokines, TNF-alpha and IL-1beta (P < 0.05), but increased the levels of the anti-inflammatory cytokine, IL-10 (P < 0.05). Another aspect of immune function, delayed type hypersensitivity (DTH) response, was decreased during and after CLA supplementation (P < 0.05). However, plasma glucose, lipids, lymphocyte phenotypic results were not affected significantly by CLA. CONCLUSION: This is the first study to show that CLA, a fatty acid naturally found in dairy and meat products, can beneficially affect immune function in healthy human volunteers. SPONSORSHIP: This study was supported by Loders-Croklaan, The Netherlands and SEERAD (Scottish Executive Environmental Rural and Agriculture Department).

Adult↗
PubMed2001

Cytokines and cytokine inducers stimulate prostaglandin E2 entry into the brain.

Cytokine inducers and cytokines increase the circulating level of prostaglandin E2 (PGE2) during the acute-phase immune response. This occurs simultaneously with the onset of fever, indicating that brain levels of PGE2 also increase. This raises the possibility that PGE2 produced in the peripheral circulation, not necessarily at distant sites from the brain, may penetrate the brain and be present in the cerebrospinal fluid (CSF). Blood and CSF levels of PGE2 in rabbits were measured by radioimmunoassay during fever stimulated in response to lipopolysaccharide (LPS), polyinosinic:polycytidylic acid (poly I:C) and interleukin-1 (IL-1) given i.v. The effect of the prostaglandin synthesis inhibitor ketoprofen on these parameters was also studied. In addition, the level of radioactivity in the CSF was measured following the administration of [125I]-labelled PGE2 i.v. during fever induced by LPS, poly I:C, IL-1 or tumor necrosis factor alpha (TNFalpha). Both LPS and poly I:C stimulated an increase in plasma and CSF levels of PGE2 over a 5-h period with a peak at 60 min and 90 min, respectively, which occurred in parallel with the changes in body temperature. Ketoprofen abolished the rise in plasma and CSF PGE2 levels and the rise in body temperature in response to LPS, poly I:C and IL-1. In experiments where animals were given [125I]-labelled PGE2 i.v., radioactivity well above the background level was measured in samples of CSF collected from LPS-, poly I:C-, IL-1- or TNFalpha-pretreated animals. In contrast the radioactivity present in samples of CSF perfusate collected from control (saline-treated) animals was indistinguishable from the background level. These data indicate that cytokine inducers and cytokines increase the mass level of PGE2 in blood and CSF and also increases the entry, from the peripheral circulation, of radiolabelled PGE2 into the third cerebral ventricle.

Acute-Phase Reaction↗
PubMed1999

Fatty acids and endothelial cell function: regulation of adhesion molecule and redox enzyme expression.

Different types of dietary fatty acids have distinct, and sometimes opposing, effects on endothelial cell function. Long-chain n-3 polyunsaturated fatty acids from fish oil (eicosapentaenoic-acid-20:5n-3 and docosahexaenoic-acid-22:6n-3) attenuate cytokine-induced adhesion molecule expression (mRNA and protein) while the n-6 polyunsaturated fatty acid arachidonic acid (eicosatetraenoic-acid-20:4n-6) either has no effect, or elicits as up- or down-regulation. Conjugated linoleic acids derived from 18:2n-6, linoleic acid also reduced the expression of adhesion molecules. These polyunsaturated fatty acids also induced redox enzyme expression (mRNA and protein) in endothelial cells and modulation of redox-sensitive transcription factors (e.g. nuclear factor kappa B, activated protein-1) which regulate the gene expression of adhesion molecules, redox enzymes and various stress proteins. The induction of redox enzyme expression by n-3 polyunsaturated fatty acids and conjugated linoleic acids could explain their inhibitory effects on gene transcription and adhesion molecule protein expression. Individual adhesion molecule genes and transcription factors appear to differ in their responsiveness to various oxidant stimuli and non-redox, more direct regulatory mechanisms (e.g. peroxisome proliferator activation receptor activation) might also be involved in their regulation.

Animals↗
PubMed1998

Prostaglandin and fatty acid modulation of Escherichia coli O157 phagocytosis by human monocytic cells.

Phagocytosis by human monocytes is an important primary survival mechanism particularly during bacterial infection. However, the processes that control the events and mediators involved in the activation of monocytes and their impact on the phagocytosis of bacteria are poorly understood. The effect of bacterial endotoxin, interleukin-1 beta (IL-1 beta), fatty acids and prostaglandin E2 (PGE2) on the phagocytosis of fluoroscein isothiocyanate (FITC)-labelled Escherichia coli (O157) by human blood monocytes and U937 cells was studied by flow cytometry. Endotoxin increased the phagocytosis of labelled bacteria by both monocytes and U937 cells. IL-1 beta and the polyunsaturated fatty acids; dihomo-gamma-linolenic and arachidonic acids also increased the phagocytic activity of both monocytes and U937 cells. In contrast, PGE2 suppressed phagocytosis in a concentration-dependent manner. The cyclo-oxygenase inhibitor, ketoprofen, further enhanced the increased phagocytic activity in the presence of endotoxin and interleukin-1 (IL-1) indicating suppression by endogenous prostaglandins. This was confirmed by the data which showed that lipopolysaccharide (LPS) and IL-1 increased PGE2 release and ketoprofen inhibited release. Endotoxin and fatty acids increased IL-1 beta release also, whereas PGE2 inhibited release. The data suggest that phagocytic activity may be linked to changes in IL-1 levels. The data presented in this study also suggest that monocyte phagocytosis in the course of bacterial infection would be altered during pathophysiological events which result in elevation of extracellular fatty acids.

Cell Culture Techniques↗
PubMed1994

Inhibition of cytokine-stimulated thymic lymphocyte proliferation by fatty acids: the role of eicosanoids.

The effect of individual fatty acids on the proliferation of thymic lymphocytes in response to interleukin-1 (IL-1) was investigated. Proliferation was estimated by measuring [3H]thymidine incorporation into the acid insoluble fraction of the thymocytes. A concentration-dependent inhibition (in the range 1-100 microM) in the IL-1-stimulated proliferation was observed with the C20 fatty acids dihomo-gamma-linolenic acid (DGLA), arachidonic acid and eicosapentaenoic acid (EPA). A less pronounced concentration-dependent inhibitory response was observed with the C18 fatty acids linoleic acid, alpha-linolenic acid and gamma-linolenic acid. Palmitic acid and oleic did not have any effect on either basal or IL-1-stimulated proliferation at concentrations up to 100 microM. The potencies of each fatty acid for this effect at a concentration of 100 microM were: arachidonic acid > EPA > or = DGLA > linoleic acid. DGLA, arachidonic acid and EPA also attenuated IL-2-stimulated proliferation. The inhibitory action of these fatty acids was not mediated by conversion to prostaglandins or other eicosanoids as the cyclooxygenase inhibitor, ketoprofen and NDGA did not alter their action. Incubation of thymocytes with radiolabelled DGLA and EPA followed by reverse-phase HPLC analysis revealed that DGLA is predominantly converted to a more polar metabolite which is not PGE1 whereas EPA does not appear to be converted to any other detectable metabolite. The data indicate that the inhibitory actions of fatty acids on cell proliferation do not occur as a result of conversion to other metabolites but may be direct effects. The inhibition of cytokine-stimulated lymphocyte proliferation by unsaturated fatty acids would imply that they may attenuate cell-mediated immune reactions.

8,11,14-Eicosatrienoic Acid↗
PubMed1994

Lipid metabolism.

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Clinical Trials as Topic↗
PubMed1993

Fatty acid modulation of cytokine release from human monocytic cells.

The effect of individual fatty acids on the release of interleukin-1-like (IL-1-like) cytokine activity was investigated on human monocytic cells, primarily the cell line U937 and also peripheral blood monocytes. IL-1-like bioactivity was estimated by assessing the effect of supernatants from monocytic cells on the proliferation of thymocytes as measured by [3H]thymidine incorporation into the acid insoluble fraction of the thymocytes. A pronounced concentration-dependent increase (in the range 1-100 microM) in the release of IL-1-like activity was observed with arachidonic acid, dihomo-gamma-linolenic acid (DGLA) and eicosapentaenoic acid (EPA) in absence and presence of bacterial endotoxin (LPS). A much less pronounced concentration-dependent increase in the release of IL-1-like activity was observed with oleic acid and linoleic acid had only a small effect at 100 microM. The potencies of each fatty for this effect using the EC50 concentrations were arachidonic acid > EPA > or = DGLA > linoleic acid > oleic acid with palmitic acid having no effect. The IL-1-like activity was confirmed by the attenuation of the monocytic-cell-supernatant-induced increase in thymocyte proliferation by anti-IL-1 beta antiserum. An increase in the release of anti-IL-1 beta-antiserum-precipitable radioactivity from U937 cells prelabelled with [35S]methionine then incubated with fatty acids in the presence of LPS further confirmed that IL-1 release was increased. Arachidonic acid and EPA also increased the release of IL-1-like activity from peripheral blood monocytes demonstrating that normal monocytes can respond in a similar manner and that this effect of the fatty acids is not restricted to the U937 cell line.

Arachidonic Acid↗
PubMed1993

Characterization of prostaglandin E2 receptors expressed on human monocytic leukaemic cell line, U937.

Prostaglandin E2 (PGE2) receptors of a human monocytic leukaemic cell line, U937 cells, have been identified. [3H]PGE2 binding to these cells was found to be saturable and highly specific. Scatchard analysis of binding data revealed a non-linear plot indicating the presence of two independent classes of binding sites with different affinities and capacities. The high-affinity class had Kd1 = 3.1 nM and binding capacities n1 = 0.6 fmol/10(6) cells, whereas the low-affinity class had Kd2 = 137 nM and capacities n2 = 16 fmol/10(6) cells. Incubation of U937 cells with 3 microM PGE2 stimulated a 15-fold increase in cAMP formation compared to basal levels. Prior exposure of these cells with 10 microM PGE2 for 60 min induced both homologous and heterologous desensitization of adenylate cyclase activity. PGE2 (3 microM) or histamine (100 microM) showed reduced stimulation of cAMP formation in these desensitized cells compared to controls. The desensitized cells also showed 80% reduction of specific PGE2 binding compared to control cells. Our data suggest that U937 cells have PGE2 receptors which are linked to the adenylate cyclase system.

Adenylyl Cyclases↗
PubMed1992

Regulation of prostaglandin E2 binding to a murine macrophage cell line, P388D1, by insulin.

Preincubation of murine macrophage-like P388D1 cells with physiological amounts of insulin resulted in an increase in prostaglandin E2 binding to these cells, by approximately 2-fold, when compared to untreated cells. Scatchard analysis of the binding of PGE2 to insulin-treated cells indicated that the enhanced binding was due to an increase in receptor number (from 0.30 +/- 0.02 to 0.63 +/- 0.03 fmol/10(6) cells for the high affinity receptor binding sites, and from 2.4 +/- 0.31 to 5.0 +/- 0.41 fmol/10(6) cells for the low affinity receptor binding sites) rather than to an increase in the affinity of the binding sites. The insulin-stimulation of PGE2 binding appeared to be associated with a lowering of the cAMP level in these cells; treatment of cells with insulin lowered the cAMP level by increasing the cAMP phosphodiesterase activity of both the membrane and cytosolic fractions. However, enhanced PGE2 binding to the cells resulted in an increase in cAMP level in the cells. This increase in cAMP level may help to enhance the immunosuppressive action of this prostanoid, as PGE2 is known to suppress many steps in the immune response, including interleukin-1 expression, by raising cAMP levels via activation of receptor-linked adenylate cyclase. Our data suggest that insulin at physiological concentrations may enhance the immunosuppressive action of PGE2.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1992

Interleukin-1 inhibits PGE2 binding to macrophage-like P388D1 cells by a cyclic AMP-independent process.

The interaction between interleukin IL-1 alpha and PGE2 on P388D1 cells has been investigated. Preincubation of murine macrophage-like cells, P388D1, with IL-1 alpha (0-73 pM) reduced the binding of PGE2 to these cells in a concentration-dependent manner. Scatchard analysis showed that IL-1 alpha decreased the PGE2 binding by lowering both the high and low affinity receptor binding capacities (from 0.31 +/- 0.02 to 0.12 +/- 0.01 fmol/10(6) cells for the high affinity receptor binding sites and from 2.41 +/- 0.12 to 1.51 +/- 0.21 fmol/10(6) cells for the low affinity receptor binding sites). However, the dissociation constants of the receptors of the IL-1 alpha-treated cells remained unchanged. Inhibition of PGE2 binding by IL-1 alpha did not involve changes in either protein phosphorylation or intracellular cyclic AMP levels. Our data clearly show that IL-1 alpha inhibits the binding of PGE2 to monocytes/macrophages and may thereby counter the immunosuppressive actions of PGE2.

Animals↗