Increased α-linolenic acid intake lowers C-reactive protein, but has no effect on markers of atherosclerosis Obesity modifies the association between plasma phospholipid polyunsaturated fatty acids and markers of inflammation: the Multi-Ethnic Study of Atherosclerosis Fish oil in combination with high or low intakes of linoleic acid lowers plasma triacylglycerols but does not affect other cardiovascular risk markers in healthy men. The effect of diet enriched with alpha-linolenic acid on soluble cellular adhesion molecules in dyslipidaemic patients. Influence of dietary supplementation with long-chain n−3 or n−6 polyunsaturated fatty acids on blood inflammatory cell populations and functions and on plasma soluble adhesion molecules in healthy adults Dietary alpha-linolenic acid inhibits proinflammatory cytokine production by peripheral blood mononuclear cells in hypercholesterolemic subjects. Reduced ex vivo interleukin-6 production by dietary fish oil is not modified by linoleic acid intake in healthy men. Virgin olive oil, palm olein and coconut oil diets do not raise cell adhesion molecules and thrombogenicity indices in healthy Malaysian adults Allopurinol Use Yields Potentially Beneficial Effects on Inflammatory Indices in Those With Recent Ischemic Stroke: A Randomized, Double-Blind, Placebo-Controlled Trial Acute reactant cytokines and neutrophil adhesion after warm ischemia in cirrhotic and noncirrhotic human livers Background diet influences the anti-inflammatory effect of alpha-linolenic acid in dyslipidaemic subjects. Sheep cheese naturally enriched in α-linolenic, conjugated linoleic and vaccenic acids improves the lipid profile and reduces anandamide in the plasma of hypercholesterolaemic subjects. Inflammatory cytokines, endothelial markers and adhesion molecules in rheumatoid arthritis: effect of intensive anti-inflammatory treatment Effect of multiple micronutrient supplementation during pregnancy on inflammatory markers in Nepalese women. Plasma inflammatory and vascular homeostasis biomarkers increase during human pregnancy but are not affected by oily fish intake. Docosahexaenoic acid-enriched canola oil increases adiponectin concentrations: a randomized crossover controlled intervention trial. Associations of alpha-linolenic acid and linoleic acid with risk factors for coronary heart disease Supplementation with Resveratrol and Curcumin Does Not Affect the Inflammatory Response to a High-Fat Meal in Older Adults with Abdominal Obesity: A Randomized, Placebo-Controlled Crossover Trial. No difference in platelet activation or inflammation markers after diets rich or poor in vegetables, berries and apple in healthy subjects An increase in dietary n-3 fatty acids decreases a marker of bone resorption in humans Increased diffusion of soluble adhesion molecules in meningitis, severe sepsis and systemic inflammatory response without neurological infection is associated with intrathecal shedding in cases of meningitis Conjugated linoleic acid supplementation for 8 weeks does not affect body composition, lipid profile, or safety biomarkers in overweight, hyperlipidemic men. The effect of dietary walnuts compared to fatty fish on eicosanoids, cytokines, soluble endothelial adhesion molecules and lymphocyte subsets: a randomized, controlled crossover trial.
Objective : To investigate the effects of increased alpha-linolenic acid (ALA)-intake on intima – media thickness ( IMT ) , oxidized low-density lipoprotein ( LDL ) antibodies , soluble intercellular adhesion molecule-1 ( sICAM-1 ) , C-reactive protein ( CRP ) , and interleukins 6 and 10 . Design : R and omized double-blind placebo-controlled trial . Subjects : Moderately hypercholesterolaemic men and women ( 55±10 y ) with two other cardiovascular risk factors (n=103).Intervention : Participants were assigned to a margarine enriched with ALA ( fatty acid composition 46 % LA , 15 % ALA ) or linoleic acid ( LA ) ( 58 % LA , 0.3 % ALA ) for 2 y. Results : Dietary ALA intake was 2.3 en% among ALA users , and 0.4 en% among LA users . The 2-y progression rate of the mean carotid IMT  ( ALA and LA : + 0.05 mm ) and femoral IMT ( ALA:+0.05 mm ; LA:+0.04 mm ) was similar , when adjusted for confounding variables . After 1 and 2 y , ALA users had a lower CRP level than LA users ( net differences −0.53 and −0.56 mg/l , respectively , P<0.05 ) . No significant effects were observed in oxidized LDL antibodies , and levels of sICAM-1 , interleukins 6 and 10 . Conclusions : A six-fold increased ALA intake lowers CRP , when compared to a control diet high in LA . The present study found no effects on markers for atherosclerosis . Sponsorship : The Dutch ‘ Praeventiefonds ’ Background and objective : Systemic inflammation is a well-known risk factor for diseases such as atherosclerosis and is augmented by the presence of obesity . In addition , it has been shown that inflammation may be negatively influenced by certain macronutrients , specifically the omega-3 and omega-6 fatty acids . The primary aim of this study is to determine whether obesity modifies the association between plasma phospholipid polyunsaturated fatty acids ( PUFAs ) and markers of inflammation and endothelial activation in Multi-Ethnic Study of Atherosclerosis ( MESA ) participants .Subjects : A sample of 2848 adults ( 25 % African American , Chinese , Hispanic , and White ) r and omly selected from the MESA cohort . Measurements : Relative plasma PUFA concentrations were determined using gas chromatography-flame ionization detection . Levels of three inflammatory markers ( high-sensitivity C-reactive protein , interleukin (IL)-6 and tumor necrosis factor-receptor 1 ) and two endothelial activation markers ( soluble intercellular adhesion molecule-1 ( sICAM-1 ) and E-selectin ) were determined with enzyme immunoassays . Linear regression analysis was used to evaluate the relationship between these markers and plasma PUFAs . Results : Obesity modified the associations of linoleic acid ( Pint=0.01 ) , dihomo-γ-linolenic ( Pint=0.07 ) and eicosapentaenoic acid ( EPA ) ( Pint=0.04 ) with sICAM-1 concentrations ; in addition , obesity modified the association of IL-6 with dihomo-γ-linolenic ( Pint=0.01 ) . In obese individuals  , sICAM-1 was inversely related to EPA levels ( P=0.02 ) , but directly related to linoleic acid levels ( P<0.001 ) . Conversely , sICAM-1 was inversely related to linoleic acid levels in normal weight individuals ( P=0.04 ) . IL-6 concentrations were significantly and directly related to dihomo-γ-linolenic acid ( DGLA ) in normal weight ( P=0.01 ) and obese participants ( P<0.001 ) , but the scale of increase across tertiles was greater in obese adults . Main effects of fatty acid and inflammatory marker associations are also reported . Conclusion : The modifying effect of obesity on the association of plasma PUFAs with IL-6 and sICAM-1 suggests differences in fatty acid metabolism and may also have implication s in dietary fatty acid intake for obese individuals , particularly for linoleic and EPAs . Further study is warranted to confirm and explain the strong associations of DGLA with inflammatory and endothelial activation markers Both ( n-3 ) long-chain PUFA ( LCPUFA ) and linoleic acid [ LA , 18:2(n-6 ) ] improve cardiovascular disease ( CVD ) risk factors , but a high-LA intake may weaken the effect of ( n-3 ) LCPUFA . In a controlled , double-blind , 2 x 2-factorial 8-wk intervention , we investigated whether fish oil combined with a high- or low-LA intake affects overall CVD risk profile .  Healthy men ( n = 64 ) were r and omized to 5 mL/d fish oil capsules ( FO ) [ mean intake 3.1 g/d ( n-3 ) LCPUFA ] or olive oil capsules ( control ) and to oils and spreads with either a high ( S/B ) or a low ( R/K ) LA content , result ing in a 7.3 g/d higher LA intake in the S/B groups than in the R/K groups . Diet , ( n-3 ) LCPUFA in peripheral blood mononuclear cells , blood pressure ( BP ) , heart rate ( HR ) , and plasma CVD risk markers were measured before and after the intervention . FO lowered fasting plasma triacylglycerol ( TAG ) ( P < 0.001 ) by 51 % and 19 % in the FO+R/K-group and FO+S/B-group , respectively , which was also reflected in postpr and ial TAG measured after the intervention ( P < 0.01 ) . Although a fat x FO interaction was found for monocyte chemoattractant protein-1 , neither the FO nor fat intervention affected fasting plasma cholesterol , glucose , insulin , fibrinogen , C-reactive protein , interleukin-6 , vascular cell adhesion molecule-1 , P-selectin , oxidized LDL , cluster of differentiation antigen 40 lig and ( CD40L ) , adiponectin , or fasting or postpr and ial BP or HR after adjustment for body weight changes . In conclusion , neither fish oil supplementation nor the LA intake had immediate pronounced effects on the overall CVD risk profile  in healthy men , but fish oil lowered plasma TAG in healthy subjects with initially low concentrations BACKGROUND Leukocyte adhesion and transendothelial migration , the critical pathogenic components in the development of atherosclerotic lesions , are largely mediated by cellular adhesion molecules ( CAMs ) . We examined whether dietary supplementation with alpha-linolenic acid ( ALA , 18:3n-3 ) affects the levels of soluble forms of CAMs in dyslipidaemic patients . METHODS We recruited 90 male dyslipidaemic patients ( mean age=51+/-8 years ) following a typical Greek diet . They were r and omly assigned either to 15 ml of linseed oil ( rich in ALA ) per day ( n=60 ) or to 15 ml of safflower oil ( rich in linoleic acid [ LA , 18:2n-6 ] ) per day ( n=30 ) . The ratio of n-6:n-3 in linseed oil supplemented group was 1.3:1 and in safflower oil supplemented group 13.2:1 . Dietary intervention lasted for 12 weeks . Blood lipids , soluble intercellular adhesion molecule-1 ( sICAM-1 ) , soluble vascular cell adhesion molecule-1 ( sVCAM-1 ) and soluble E-selectin ( sE-selectin ) were measured . RESULTS Dietary supplementation with ALA significantly decreased sVCAM-1 levels ( median decrease 18.7 % [ 577.5 ng/ml versus 487 ng/ml , P=0.0001 ] ) . In the LA supplemented group , sVCAM-1 was also significantly decreased but to a lesser extent ( median decrease 10.6 % [ 550.5 ng/ml versus 496 ng/ml , P=0.0001 ] ) . After controlling for smoking habits , no significant difference was observed in the reduction of sVCAM-1 levels between the two treatment arms ( P=0.205 ) . The decrease of sVCAM-1 was independent of lipid changes in both groups . CONCLUSIONS Dietary supplementation with ALA for 12 weeks significantly decreases sVCAM-1 levels in dyslipidaemic patients . This effect presents a potential mechanism for the beneficial effect of plant n-3 polyunsaturated fatty acids in the prevention of coronary artery disease . In addition , dietary supplementation with LA significantly decreases sVCAM-1 levels , an effect which requires further investigation Greatly increasing the amounts of flaxseed oil [ rich in α-linolenic acid ( ALNA ) ] or fish oil ( FO ) ; [ rich in eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) ] in the diet can decrease inflammatory cell functions and so might impair host defense . The objective of this study was to determine the effect of dietary supplementation with moderate levels of ALNA , γ-linolenic acid ( GLA ) , arachidonic acid ( ARA ) , DHA , or FO on inflammatory cell numbers and functions and on circulating levels of soluble adhesion molecules .  Healthy subjects aged 55 to 75 yr consumed nine capsules per day for 12 wk . The capsules contained placebo oil ( an 80∶20 mix of palm and sunflowerseed oils ) or blends of placebo oil with oils rich in ALNA , GLA , ARA , or DHA or FO . Subjects in these groups consumed 2 g ALNA ; approximately 700 mg GLA , ARA , or DHA ; or 1 g EPA plus DHA ( 720 mg EPA+280 mg DHA ) daily from the capsules . Total fat intake from the capsules was 4 g per day . None of the treatments affected inflammatory cell numbers in the bloodstream ; neutrophil and monocyte phagocytosis or respiratory burst in response to E. coli ; production of tumor necrosis factor-α , interleukin-1β , and interleukin-6 in response to bacterial lipopolysaccharide ; or plasma concentrations of soluble intercellular adhesion molecule-1 . In contrast , the ALNA and FO treatments decreased the plasma concentrations of soluble vascular cell adhesion molecule-1 ( 16 and 28 % decrease , respectively ) and soluble E-selectin ( 23 and 17 % decrease , respectively ) . It is concluded that , in contrast to previous reports using higher amounts of these fatty acids , a moderate increase in consumption of long-chain n−6 or n−3 polyunsaturated fatty acids does not significantly affect inflammatory cell numbers or neutrophil and monocyte responses in humans and so would not be expected to cause immune impairment . Furthermore , we conclude that moderate levels of ALNA and FO , which could be incorporated into the diet , can decrease some markers of endothelial activation and that this mechanism of action may contribute to the reported health benefits of n−3 fatty acids BACKGROUND Atherosclerosis is a chronic inflammatory disease . We previously reported that a diet high in alpha-linolenic acid ( ALA ) reduces lipid and inflammatory cardiovascular disease risk factors in hypercholesterolemic subjects . OBJECTIVE The objective was to evaluate the effects of a diet high in ALA on serum proinflammatory cytokine concentrations and cytokine production by cultured peripheral blood mononuclear cells ( P BMC s ) from subjects fed the experimental diets . DESIGN A r and omized , controlled , 3-diet , 3-period crossover study design was used . Hypercholesterolemic subjects ( n = 23 ) were assigned to 3 experimental diets : a diet high in ALA ( ALA diet ; 6.5 % of energy ) , a diet high in linoleic acid ( LA diet ; 12.6 % of energy ) , and an average American diet ( AAD ) for 6 wk . Serum interleukin (IL)-6 , IL-1beta , and tumor necrosis factor-alpha ( TNF-alpha ) concentrations and the production of IL-6 , IL-1beta , and TNF-alpha by P BMC s were measured . RESULTS IL-6 , IL-1beta , and TNF-alpha production by P BMC s and serum TNF-alpha concentrations were lower ( P < 0.05 and P < 0.08 , respectively ) with the ALA diet than with the LA diet or AAD .  P BMC production of TNF-alpha was inversely correlated with ALA ( r = -0.402 , P = 0.07 ) and with eicosapentaenoic acid ( r = -0.476 , P = 0.03 ) concentrations in P BMC lipids with the ALA diet . Changes in serum ALA were inversely correlated with changes in TNF-alpha produced by P BMC s ( r = -0.423 , P < 0.05 ) . CONCLUSIONS Increased intakes of dietary ALA elicit antiinflammatory effects by inhibiting IL-6 , IL-1beta , and TNF-alpha production in cultured P BMC s. Changes in P BMC ALA and eicosapentaenoic acid ( derived from dietary ALA ) are associated with beneficial changes in TNF-alpha release . Thus , the cardioprotective effects of ALA are mediated in part by a reduction in the production of inflammatory cytokines Fish oil ( FO ) is considered antiinflammatory , but evidence regarding its effect on human cytokine production is conflicting . High linoleic acid ( LA ) intake may impair any effects of FO . The aim of this study was to investigate how FO combined with high or low LA intake affected ex vivo cytokine production from cultures of whole blood , peripheral blood mononuclear cells ( P BMC ) , and monocytes in healthy men . The study was a double-blinded , controlled , 2 x 2 factorial 8-wk intervention . Sixty-four healthy men were r and omized to 5 mL/d FO or olive oil ( OO ) provided in capsules and to spreads and oils with high or low LA content , result ing in LA intakes of 7 + /- 2 % and 4 + /- 1 % energy , respectively . We measured eicosapentaenoic acid ( EPA ) in P BMC and stimulated cytokine production in whole blood and P BMC 24-h cultures before and immediately after intervention and after an 8-wk wash-out period , and in monocyte cultures immediately after intervention . P BMC -EPA was markedly increased by FO ( P < 0.001 ) . LA intake did not modify the incorporation of FO and tended to have only a slight effect on P BMC -EPA by itself ( P = 0.06 ) . Lipopolysaccharide (LPS)-stimulated whole-blood interleukin (IL)-6 production immediately after intervention was lower with FO than OO ( P = 0.02 ) but did not correlate with P BMC -EPA in the FO groups ( r = -0.12 ; P = 0.53 ; n = 31 ) . The LA intake did not modify IL-6 production or the effect of FO . Neither FO nor LA intake affected the production of tumor necrosis factor-alpha , IL-10 , or interferon-gamma in any of the cultures . In conclusion , FO intake reduced IL-6 production from LPS-stimulated whole blood in healthy men compared with OO , but the effect was not modified by the LA intake Background / objectives : Effects of high-protein diets that are rich in saturated fats on cell adhesion molecules , thrombogenicity and other nonlipid markers of atherosclerosis in humans have not been firmly established . We aim to investigate the effects of high-protein Malaysian diets prepared separately with virgin olive oil ( OO ) , palm olein ( PO ) and coconut oil ( CO ) on cell adhesion molecules , lipid inflammatory mediators and thromobogenicity indices in healthy adults . Methods : A r and omized cross-over intervention with three dietary sequences , using virgin OO , PO and CO as test fats , was carried out for 5 weeks on each group consisting of 45 men and women . These test fats were incorporated separately at two-thirds of 30 % fat calories into high-protein Malaysian diets . Results : For fasting and nonfasting blood sample s , no significant differences were observed on the effects of the three test-fat diets on thrombaxane B2 ( TXB2 ) , TXB2/PGF1α ratios and soluble intracellular and vascular cell adhesion molecules . The OO diet induced significantly lower ( P<0.05 ) plasma leukotriene B4 ( LTB4 ) compared with the other two test diets , whereas PGF1α concentrations were significantly higher ( P<0.05 ) at the end of the PO diet compared with the OO diet . Conclusion : Diets rich in saturated fatty acids from either PO or CO and high in monounsaturated oleic acid from virgin OO do not alter the thrombogenicity indices — cellular adhesion molecules , thromboxane B2 ( TXB2 ) and TXB2/prostacyclin ( PGF1α ) ratios . However , the OO diet lowered plasma proinflammatory LTB4 , whereas the PO diet raised the antiaggregatory plasma PGF1α in healthy Malaysian adults . This trial was registered at clinical trials.gov as NCT 00941837 Background and Purpose — Elevated serum uric acid level is associated with poor outcome and increased risk of recurrent events after stroke . The xanthine oxidase inhibitor allopurinol lowers uric acid but also attenuates expression of inflammatory adhesion molecules in murine models , reduces oxidative stress in the vasculature , and improves endothelial function . We sought to investigate whether allopurinol alters expression of inflammatory markers after acute ischemic stroke . Methods — We performed a r and omized , double-blind , placebo-controlled trial to investigate the safety , tolerability , and effect of 6 weeks ' treatment with high- ( 300 mg once a day ) or low- ( 100 mg once a day ) dose allopurinol on levels of uric acid and circulating inflammatory markers after ischemic stroke . Results — We enrolled 50 patients with acute ischemic stroke ( 17 , 17 , and 16 in the high , low , and placebo groups , respectively ) . Mean ( ±SD ) age was 70 ( ±13 ) years . Groups had similar characteristics at baseline . There were no serious adverse events . Uric acid levels were significantly reduced at both 7 days and 6 weeks in the high-dose group ( by 0.14 mmol/L at 6 weeks , P=0.002 ) . Intercellular adhesion molecule-1 concentration ( ng/mL ) rose by 51.2 in the placebo group , rose slightly ( by 10.6 ) in the low-dose allopurinol group , but fell in the high-dose group ( by 2.6 ; difference between groups P=0.012 , Kruskal-Wallis test ) . Conclusion — Allopurinol treatment is well tolerated and attenuates the rise in intercellular adhesion molecule-1 levels seen after stroke . Uric acid levels were lowered with high doses . These findings support further evaluation of allopurinol as a preventive measure after stroke Animal studies suggest that acute phase reactant cytokines and polymorphonuclear leukocytes ( PMN ) may play a critical role in ischemia‐ reperfusion injury . To evaluate whether similar mechanisms are operative in human liver , six cirrhotic and nine noncirrhotic patients undergoing right hepatectomy were r and omized for utilization of hepatic vascular exclusion ( HVE ) as a model of ischemia‐reperfusion injury . Portal and systemic levels of acute reactant cytokines ( interleukin 6 [ IL‐6 ] , interleukin 1 [ IL‐1 ] , tumor necrosis factor α [ TNF‐α ] ) and neutrophil adhesion in serial liver biopsy specimens were studied . Correlations among mediators , leukocyte adhesion , and markers of liver injury were also evaluated . Hepatic vascular exclusion result ed in substantial and reproducible changes in portal and arterial IL‐6 levels in both cirrhotic and noncirrhotic patients . Portal and systemic cytokine levels were comparable in most instances , whereas levels were usually higher in cirrhotic patients than in noncirrhotic patients . Negative correlations were found between IL‐6 levels at the time of reperfusion and later TNF‐α levels . IL‐6 levels correlated negatively with numerous markers of hepatocellular injury and the number of postoperative complications . Hepatic vascular exclusion increased neutrophils adhesion after reperfusion in cirrhotic patients but not in noncirrhotic patients . In cirrhotic patients , the degree of leukocyte adhesion after reperfusion correlated with several postoperative markers of liver injury . This study in humans shows that acute reactant cytokines are released during liver ischemia and , interestingly , that IL‐6 levels strongly correlate with clinical and laboratory measures of injury . Further studies to evaluate possible causal relationship with hepatic injury are warranted , with emphasis on the role of IL‐6 and PMN adhesion Long-chain n-3 PUFA from fish oils are known to have anti-inflammatory effects . We evaluated the effect of alpha-linolenic acid ( ALA ) , precursor of n-3 fatty acids , on serum inflammatory markers and soluble cellular adhesion molecules ( sCAM ) of dyslipidaemic males , relative to their background diet . Participants were assigned to two groups , based upon food intake patterns : ( a ) twenty-one dyslipidaemic subjects who habitually ate a Mediterranean-Cretan-type diet ; ( b ) nineteen dyslipidaemic subjects who normally ate a Westernised Greek diet .  All were supplemented with 8.1 g ALA/d for 12 weeks . We determined serum amyloid A ( SAA ) , C-reactive protein ( CRP ) , macrophage colony-stimulating factor ( MCSF ) , IL-6 , soluble vascular cell adhesion molecule-1 ( sVCAM-1 ) , soluble intercellular adhesion molecule-1 and soluble E-selectin concentrations at the beginning and the end of the ALA supplementation period . Serum baseline concentrations of inflammatory markers and sCAM were similar across the diet groups . Type of diet had a significant impact on the response of inflammatory markers to ALA supplementation . The Westernised Greek diet group showed a reduction in SAA ( P<0.001 ) , CRP ( P=0.002 ) , MCSF ( P=0.005 ) and IL-6 ( P=0.04 ) concentrations . The Mediterranean-Cretan-type background diet group showed a significant reduction only in MCSF concentrations ( P=0.003 ) . The sVCAM-1 concentrations were significantly reduced in both the Westernised Greek diet group ( P=0.001 ) and the Mediterranean-Cretan-type diet group ( P<0.001 ) . The present study demonstrated that ALA supplementation lowered the serum concentrations of inflammatory markers more profoundly when the background diet was rich in saturated fatty acids and poor in MUFA Intake of dairy fat has long been considered as a risk factor for CVD . Pasture and dietary lipid supplementation have been reported to be reliable strategies in ruminant nutrition , in order to increase the content of α-linolenic acid ( ALA ) , conjugated linoleic acid ( CLA ) and vaccenic acid ( VA ) , and decrease SFA in milk fat . In the present study , we aim ed at verifying whether consumption of a sheep cheese , naturally enriched in ALA , CLA and VA , would modify the plasma lipid and endocannabinoid profiles in mildly hypercholesterolaemic subjects . A total of forty-two adult volunteers ( nineteen males and twenty-three females ) with diagnosed mildly hypercholesterolaemia ( total cholesterol 5·68 - 7·49 mmol/l ) were r and omly assigned to eat 90 g/d of a control or enriched cheese for 3 weeks , with a cross-over after 3 weeks of  washout . Plasma lipids , endocannabinoids , adipokines and inflammatory markers were measured . The intake of enriched cheese significantly increased the plasma concentrations of CLA , VA , the n-3 fatty acids ALA and EPA , and more remarkably decreased that of the endocannabinoid an and amide . LDL-cholesterol decreased significantly ( 7 % ) . No changes were detected in the levels of inflammatory markers ; however , a significant correlation was found between the plasma levels of an and amide and leptin . The control cheese modified none of the parameters measured . The results obtained do not support the view that intake of dairy fat is detrimental to hypercholesterolaemic subjects . Indeed , they show that a naturally enriched cheese possesses beneficial properties , since it ameliorates the plasma lipid profile , and more remarkably reduces endocannabinoid bio synthesis Tumour necrosis factor alpha ( TNF-α ) and interlekin-6 ( IL-6 ) are key inflammatory cytokines in the pathogenesis of rheumatoid arthritis ( RA ) , a disease also associated with endothelial perturbation and increased serum levels of adhesion molecules . As relationships between these processes and molecules are unclear , we tested the hypotheses ( a ) that TNF-α and IL-6 are linked to endothelial activation/damage and levels of soluble adhesion molecules , and ( b ) that intensive anti-inflammatory treatment improves levels of these indices . We recruited 66 patients with RA , 48 community controls ( CC ) , and 25 disease controls ( DC ) .  Plasma TNF-α and IL-6 were compared to markers of vascular biology ( vWF , sE-sel ) , soluble adhesion molecules ( sICAM , sVCAM ) and routine inflammatory markers ( CRP and ESR ) . Blood was obtained at baseline and at 1 week and again 4 weeks after anti-inflammatory treatment in a subgroup of 29 patients with RA . With the exception of sE-selectin , RA patients had increased levels of all plasma markers compared to the HCs , whilst levels in the DCs were largely intermediate between RA and the CCs . Within the RA group , sEsel correlated with both CRP and ESR whilst TNF-α correlated with sVCAM ( all r > 0.32 , P < 0.01 ) . After 1 week of combined anti-inflammatory therapy , only CRP , ESR , sEsel and sVCAM were significantly reduced ( all P < 0.05 ) . In RA , endothelial activation ( as sEsel ) correlates with classical markers of inflammation and is reduced by intensive anti-inflammatory medications BACKGROUND Multiple micronutrient supplementation of Nepalese women during pregnancy is associated with a significant increase in birth weight . OBJECTIVE We tested the hypothesis that improved birth weight in infants of mothers supplemented with micronutrients is associated with a decrease in inflammatory responses and an increase in the production of T helper 1 cells and T helper 2 cells . DESIGN The study was embedded in a r and omized controlled trial of 15 micronutrients , compared with iron-folate supplementation ( control ) , given during pregnancy with the aim of increasing birth weight . Blood sample s were collected at 32 wk of gestation , 12 - 20 wk after supplementation began , for the measurement of inflammatory markers . Breast-milk sample s were collected 1 mo after delivery for the measurement of the ratio of milk sodium to potassium ( milk Na : K ) . In an opportunistically selected subgroup of 70 women , mitogen-stimulated cytokine production was measured ex vivo in whole blood . RESULTS Blood eosinophils ; plasma concentrations of the acute phase reactants C-reactive protein , alpha(1)-acid glycoprotein ( AGP ) , neopterin , and ferritin ; milk Na : K ; and the production of interleukin ( IL ) 10 , IL-4 , interferon gamma , and tumor necrosis factor alpha in whole blood did not differ significantly between the supplemented and control groups . Plasma C-reactive protein and AGP were higher in women who had a preterm delivery , and AGP was higher in women who delivered a low-birth-weight term infant than in women who delivered a normal-birth-weight term infant . CONCLUSIONS The results indicate an association between systemic inflammation in late pregnancy and compromised delivery outcome in Nepalese women but do not support the hypothesis that multiple micronutrient supplementation changes cytokine production or inflammatory markers The Salmon in Pregnancy Study investigated whether the increased consumption of ( n-3 ) long-chain PUFA ( LC-PUFA ) from farmed Atlantic salmon  affects immune function during pregnancy and atopic disease in neonates compared with a habitual diet low in oily fish . In this context , because the ingestion of ( n-3 ) LC-PUFA may lower the concentrations of inflammatory biomarkers , we investigated whether the consumption of oily fish affects the levels of inflammatory cytokines and vascular adhesion factors during pregnancy . Pregnant women ( n = 123 ) were r and omly assigned to continue their habitual diet ( control group , n = 61 ) , which was low in oily fish , or to consume two 150-g salmon portions/wk ( salmon group , n = 62 ; providing 3.45 g EPA plus DHA ) from 20 wk of gestation until delivery . Plasma inflammatory cytokines and vascular adhesion factors were measured in maternal plasma sample s. Inflammatory biomarkers , including IL-8 , hepatocyte growth factor , and monocyte chemotactic protein , increased over the course of pregnancy ( P < 0.001 ) , whereas plasma matrix metalloproteinase 9 , IL-6 , TNFα , and nerve growth factor concentrations were not affected . Vascular homeostasis biomarkers soluble E-selectin , soluble vascular adhesion molecule-1 , soluble intercellular adhesion molecule (sICAM)-1 , and total plasminogen activator inhibitor-1 increased as pregnancy progressed ( P < 0.001 ) . The plasma sICAM-1 concentration was greater in the control group than in the salmon group at wk 20 ( baseline ) and 38 ( P = 0.007 ) but there was no group x time interaction , and when baseline concentration was used as a covariate , the groups did not differ ( P = 0.69 ) . The remaining biomarkers analyzed were similar in both groups . Therefore , although some inflammatory and vascular homeostasis biomarkers change during pregnancy , they are not affected by the increased intake of farmed salmon BACKGROUND AND AIMS Little is known about the effect of various dietary fatty acids on pro- and anti-inflammatory processes . We investigated the effect of 5 oils containing various amounts of alpha-linolenic acid ( ALA ) , linoleic acid ( LA ) , oleic acid ( OA ) and docosahexaenoic acid ( DHA ) on plasma inflammatory biomarkers and expression levels of key inflammatory genes and transcription factors in whole blood cells . METHODS AND RESULTS In a r and omized , crossover controlled nutrition intervention , 114 adult men and women with abdominal obesity and at least one other criterion for the metabolic syndrome consumed 5 experimental isoenergetic diets for 4 weeks each , separated by 4-week washout periods . Each diet provided 60 g/3000 kcal of different oils : 1 ) control corn/safflower oil blend ( CornSaff ; LA-rich ) , 2 ) flax/safflower oil blend ( FlaxSaff ; ALA-rich ) , 3 ) conventional canola oil ( Canola ; OA-rich ) , 4 ) high oleic canola oil ( CanolaOleic ; highest OA content ) , 5 ) DHA-enriched high oleic canola oil ( CanolaDHA ; OA- and DHA-rich ) . Gene expression in whole blood cells was assessed in a subset of 62 subjects .  CanolaDHA increased plasma adiponectin concentrations compared with the control CornSaff oil treatment ( + 4.5 % , P = 0.04 ) and FlaxSaff ( + 6.9 % , P = 0.0008 ) . CanolaDHA also reduced relative expression levels of interleukin (IL)1B compared with CornSaff and Canola ( -11 % and -13 % , respectively , both P = 0.03 ) . High-sensitivity C-reactive protein concentrations were lower after Canola than after FlaxSaff ( -17.8 % , P = 0.047 ) . CONCLUSION DHA-enriched canola oil exerts anti-inflammatory effects compared with polyunsaturated fatty acids from plant sources Background : Prevention of coronary heart disease ( CHD ) in high-risk subjects . Objective : To investigate the associations of dietary intake of alpha-linolenic acid ( ALA ) and linoleic acid ( LA ) as assessed by food frequency question naire and in the plasma cholesteryl ester ( CE ) , with CHD risk factors . Design : Baseline data of a double-blind , r and omized placebo-controlled trial . Subjects have hypercholesterolemia ( 6.0–8.0 mmol/l ) and at least two other CHD risk factors ( n=266 ) . Results : The reported  dietary ALA and LA intakes and the LA/ALA ratio were associated with the contents in the CE ( r=0.37 , r=0.21 , and r=0.42 , respectively ; P<0.01 ) . In multivariate analysis , CE ALA was inversely associated with diastolic blood pressure ( r=−0.13 ; P<0.05 ) and positively with serum triacylglycerol ( r=0.13 ; P<0.05 ) , and CE LA was inversely associated with serum triacylglycerol ( r=−0.32 ; P<0.01 ) . The CE LA/ALA ratio was strongly inversely associated with CE ALA ( r=−0.95 ; P<0.01 ) . In the lowest quintile of CE ALA , mean dietary intake was 0.4 energy % ALA ( 1.2 g/day ) , 8.4 energy % LA and an LA/ALA ratio of 21 , and in the highest quintile 0.6 energy % ALA ( 1.7 g/day ) , 6.8 energy % LA and 12 ( ratio ) . In the lowest quintile of CE ALA the diastolic blood pressure was 4 mmHg lower ( P trend<0.05 ) , and the serum triacylglycerol 0.3 mmol/l higher ( P trend NS ) when compared with the top quintile . Conclusions : In a CHD high-risk population with LA-rich background diet , these cross-sectional data suggest that replacing LA in the diet by ALA may decrease diastolic blood pressure , and may increase serum triacylglycerol concentration . Sponsorship : Dutch Prevent fund grant no. 28 - 2757 ; Unilever (margarine).European Journal of Clinical Nutrition ( 2000 ) 54 , Background High-fat meals induce postpr and ial inflammation . Resveratrol is a polyphenol known to prevent comorbidities associated with cardiovascular disease and exerts an anti-inflammatory action . There is also an increasing body of evidence supporting the role of curcumin , a polyphenol from the curcuminoid family , as a modulator of proinflammatory processes . Objective The objectives of this study were to investigate the following : 1 ) the bioavailability of resveratrol consumed in combination with curcumin after consumption of a high-fat meal ; and 2 ) the acute combined effects of this combination on the postpr and ial inflammatory response of subjects with abdominal obesity . Methods In a double blind , crossover , r and omized , placebo-controlled study , 11 men and 11 postmenopausal women [ mean ± SD age : 62 ± 5 y ; mean ± SD body mass index ( in kg/m2 ) : 29 ± 3 ] underwent a 6-h oral fat tolerance test on 2 occasions separated by 1 - 2 wk : once after consumption of a dietary supplement ( 200 mg resveratrol and 100 mg curcumin , Res/Cur ) and once after consumption of a placebo ( cellulose ) . Plasma concentrations of total resveratrol and its major metabolites as well as inflammatory markers , adhesion molecules , and whole blood NFκB1 and PPARA gene expression were measured during both fat tolerance tests . Results Kinetics of resveratrol and identified metabolites revealed rapid absorption patterns but also relatively limited bioavailability based on free resveratrol concentrations . Supplementation with Res/Cur did not modify postpr and ial variations in circulating inflammatory markers ( C-reactive protein , IL-6 , IL-8 , monocyte chemoattractant protein-1 ) and adhesion molecules [ soluble E-selectin , soluble vascular cell adhesion molecule-1 ( sVCAM-1 ) , soluble intercellular adhesion molecule-1 ] compared to placebo ( PTreatment × Time > 0.05 ) . However , Res/Cur significantly decreased the cumulative postpr and ial response of sVCAM-1 , compared to placebo ( incremental area under the curve -4643 % , P = 0.01 ) . Postpr and ial variations of whole-blood PPARA and NFKB1 gene expression were not different between Res/Cur and placebo treatments . Conclusions Acute supplementation with Res/Cur has no impact on the postpr and ial inflammation response to a high-fat meal in abdominally obese older adults . Further studies are warranted to examine how resveratrol and curcumin may alter the vascular response to a high-fat meal . This trial was registered at clinical trials.gov as NCT01964846 Summary . Background : High intake of vegetables and fruits is associated with decreased risk of coronary heart disease . Part of these cardioprotective effects may be mediated via the antithrombotic effects of compounds found in vegetables and fruits , such as flavonoids . Aim of the study : To study the effects of high and low intake of vegetables , berries and apple on platelet function and inflammatory markers . Methods : The study was a r and omised , controlled parallel human dietary intervention with healthy female and male volunteers ( n = 77 , 19–52 y ) . Nineteen healthy volunteers served as controls . The volunteers consumed one of four strictly controlled isocaloric 6-week diets containing either 810 or 196 g/10 MJ of vegetables , berries and apple and rich either in linoleic acid ( 11 % of energy , en% ) or oleic acid ( 12 en% ) . Blood and three 24-hour urine sample s were collected at the beginning and at the end of the study period for analyses of various markers of platelet function and inflammation . Results : No differences between the treatment groups were seen in platelet count or volume , markers of platelet activation ( ex vivo aggregation to ADP and thrombin receptor activating peptide , protein kinase C activity , urinary 2,3-dinor-thromboxane B2 excretion , plasma P-selectin ) , plasma intercellular adhesion molecule-1 , sensitive C-reactive protein , or antiphospholipid antibodies . Conclusions : The results indicate that in healthy volunteers 6-week diets differing markedly in the amounts of vegetables , berries and apple do not differ in their effects on platelets or inflammation Human , animal , and in vitro research indicates a beneficial effect of appropriate amounts of omega-3 ( n-3 ) polyunsaturated fatty acids ( PUFA ) on bone health . This is the first controlled feeding study in humans to evaluate the effect of dietary plant-derived n-3 PUFA on bone turnover , assessed by serum concentrations of N-telopeptides ( NTx ) and bone-specific alkaline phosphatase ( BSAP ) .  Subjects ( n = 23 ) consumed each diet for 6 weeks in a r and omized , 3-period crossover design : 1 ) Average American Diet ( AAD ; [ 34 % total fat , 13 % saturated fatty acids ( SFA ) , 13 % monounsaturated fatty acids ( MUFA ) , 9 % PUFA ( 7.7 % LA , 0.8 % ALA ) ] ) , 2 ) Linoleic Acid Diet ( LA ; [ 37 % total fat , 9 % SFA , 12 % MUFA , 16 % PUFA ( 12.6 % LA , 3.6 % ALA ) ] ) , and 3 ) α-Linolenic Acid Diet ( ALA ; [ 38 % total fat , 8 % SFA , 12 % MUFA , 17 % PUFA ( 10.5 % LA , 6.5 % ALA ) ] ) . Walnuts and flaxseed oil were the predominant sources of ALA . NTx levels were significantly lower following the ALA diet ( 13.20 ± 1.21 nM BCE ) , relative to the AAD ( 15.59 ± 1.21 nM BCE ) ( p < 0.05 ) . Mean NTx level following the LA diet was 13.80 ± 1.21 nM BCE . There was no change in levels of BSAP across the three diets . Concentrations of NTx were positively correlated with the pro-inflammatory cytokine TNFα for all three diets . The results indicate that plant sources of dietary n-3 PUFA may have a protective effect on bone metabolism via a decrease in bone resorption in the presence of consistent levels of bone formation ObjectiveS epsis and systemic inflammatory response syndrome ( SIRS ) result in the release in plasma of inflammatory cytokines and soluble forms of adhesion molecules in relation to endothelial activation . This study was design ed to compare cerebrospinal fluid ( CSF ) concentrations of adhesion molecules in meningitis and SIRS without neurological infection and to evaluate in meningitis whether they originate from passive diffusion through damaged blood – CSF barrier or from local production . Design Prospect i ve observational study . Setting University hospital medical intensive care unit . Patients Nineteen patients with meningitis and 41 patients with sepsis or SIRS without cerebrospinal infection consecutively admitted to the critical care unit over an 18-month period . Interventions Soluble forms of adhesion molecules ( ICAM-1 , VCAM-1 , E-selectin ) and cytokines ( interleukin (IL)-1β and TNF−α ) were measured in paired CSF and blood sample s.  Results Serum concentrations of soluble adhesion molecules and cytokines were increased in the two groups , without significant differences . The CSF concentrations were elevated in both cases , whereas patients with meningitis demonstrated significantly higher CSF concentrations of soluble ICAM-1 , VCAM-1 , E-selectin , and TNF-α ( p<0.001 ) , with higher corresponding CSF/serum ratios . Correlations between CSF and serum concentrations were found only in meningitis . These correlations were strong for soluble ICAM-1 ( r2=0.7 , p<0.001 ) and E-selectin ( r2=0.9 , p<0.001 ) , but weaker for VCAM-1 . VCAM-1 CSF/serum ratios were increased , in comparison with ICAM-1 and E-selectin CSF/serum ratios , despite similar molecular weights . Serum and CSF levels of cytokines and adhesion molecules were not predictive of death for the whole population , except concentrations of ICAM-1 significantly increased in non-surviving patients ( p<0.05 ) . Conclusions The CSF soluble adhesion molecules are increased in sepsis , SIRS and meningitis . In meningitis , the correlation between CSF and serum concentrations of adhesion molecules and the presence of a discrepancy of CSF/serum ratios for molecules of the same molecular weight may suggest intrathecal shedding in addition to diffusion through blood – CSF barrier The usefulness of conjugated linoleic acid ( CLA ) as a nutraceutical remains ambiguous . Our objective was , therefore , to investigate the effect of CLA on body composition , blood lipids , and safety biomarkers in overweight , hyperlipidemic men . A double-blinded , 3-phase crossover trial was conducted in overweight ( BMI ≥ 25 kg/m(2 ) ) , borderline hypercholesterolemic [ LDL-cholesterol ( C ) ≥ 2.5 mmol/L ] men aged 18 - 60 y. During three 8-wk phases , each separated by a 4-wk washout period , 27 participants consumed under supervision in r and om order 3.5 g/d of safflower oil ( control ) , a 50:50 mixture of trans 10 , cis 12 and cis 9 , trans 11 ( c9 , t11 ) CLA : Clarinol G-80 , and c9 , t11 isomer : c9 , t11 CLA . At baseline and endpoint of each phase , body weight , body fat mass , and lean body mass were measured by DXA . Blood lipid profiles and safety biomarkers , including insulin sensitivity , blood concentrations of adiponectin , and inflammatory ( high sensitive-C-reactive protein , TNFα , and IL-6 ) and oxidative ( oxidized-LDL ) molecules , were measured . The effect of CLA consumption on fatty acid oxidation was also assessed . Compared with the control treatment , the CLA treatments did not affect changes in body weight , body composition , or blood lipids . In addition , CLA did not affect the β-oxidation rate of fatty acids or induce significant alterations in the safety markers tested . In conclusion , although no detrimental effects were caused by supplementation , these results do not confirm a role for CLA in either body weight or blood lipid regulation in humans We tested the hypothesis that walnut consumption can exert effects on markers of inflammation and endothelial activation similar to those produced by fish consumption . In a crossover dietary intervention trial , 25 normal to mildly hyperlipidemic men and women were r and omly assigned to one of three isoenergetic diets : a walnut diet incorporating 42.5 g of walnuts per 10.1 mJ 6 times per week ( 1.8 % of energy n-3 fat ) ; a fish diet providing 113 g of fatty fish per 10.1 mJ 2 times per week ( 0.8 % of energy n-3 fat ) , or a control diet ( no nuts or fish , 0.4 % of energy n-3 fat ) for 4 weeks on each diet . Both the walnut and fish diets inhibited circulating concentrations of prostagl and in E metabolite ( PGEM ) and 11-dehydro thromboxane B2 , but demonstrated no effect on blood interleukin-1β ( IL-1β ) , interleukin-6 ( IL-6 ) , tumor necrosis factor-α¯ ( TNF-α¯ ) , and C-reactive protein ( CRP ) or the number of circulating lymphocyte subsets . On the walnut diet the proportion of plasma phospholipid α¯-linolenic acid ( ALA ) increased 140 % and arachidonic acid ( AA ) decreased 7 % compared to both the control and fish diets . The proportion of plasma phospholipid eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) increased about 200 % and 900 % respectively on the fish diet relative to either the control or walnut diet . The walnut diet inhibited E-selectin by 12.7 % relative to the fish diet , and the fish diet inhibited secretory intercellular adhesion molecule-1 ( s-ICAM-1 ) by 4.5 % relative to the control diet . Both walnuts and fish in commonly consumed amounts may have modest albeit distinct effects on circulating adhesion molecules
However , subgroup and meta-regression analysis suggested that in subjects with a more profound increase of dietary LA intake , LA might increase the blood CRP level .
Other acute phase reactants including fibrinogen and plasminogen activator inhibitor-1 and adhesion molecules were not significantly changed when LA was increased in diet .
Our meta- analysis suggested that increasing dietary LA intake does not have a significant effect on the blood concentrations of inflammatory markers .
However , the extent of change in dietary LA intake might affect the effect of LA supplementation on CRP
PURPOSE The aim of the present study was to investigate the effect of increasing dietary linoleic acid ( LA ) intake on the blood concentrations of inflammatory markers including cytokines , acute phase reactants and adhesion molecules in adults .