Anti-inflammatory effects of oleic acid and the anthocyanin keracyanin alone and in combination: effects on monocyte and macrophage responses and the NF-κB pathway.

Monocyte recruitment and activation of macrophages are essential for homeostasis but are also related to the development and progression of cardiometabolic diseases. The management of inflammation with dietary components has been widely investigated. Two components that may influence inflammation are unsaturated fatty acids such as oleic acid (OA; 18:1cis-9) and antioxidant compounds like anthocyanins. Molecular and metabolic effects of such bioactive compounds are usually investigated in isolation, whereas they may be present in combination in foods or the diet. Considering this, we aimed to analyze the effects of OA and the anthocyanin keracyanin (AC) alone and in combination on toll-like receptor-mediated inflammatory responses in monocytes and macrophages. For this, THP-1-derived macrophages and monocytes were exposed to 3 treatments: OA, AC, or the combination (OAAC) and then stimulated with lipopolysaccharide. Inflammation-related gene expression and protein concentrations of IL-1ß, TNF-α, IL-6, MCP-1, and IL-10 were assessed. Also, NFκBp65, IκBα, and PPAR-γ protein expression were determined. OA, AC, and OAAC decreased pNFκBp65, PPARγ, IκBα, TNF-α, IL-1ß, IL-6, and MCP-1 and increased IL-10. MCP-1 protein expression was lower with OAAC than with either OA and AC alone. Compared to control, OAAC decreased mRNA for TLR4, IκKα, IκBα, NFκB1, MCP-1, TNF-α, IL-6, and IL-1ß more than OA or AC did alone. Also, IL-10 mRNA was increased by OAAC compared with control, OA, and AC. In summary, OA and AC have anti-inflammatory effects individually but their combination (OAAC) exerts a greater effect.

Eighteen­carbon trans fatty acids and inflammation in the context of atherosclerosis.

Endothelial dysfunction is a pro-inflammatory state characterized by chronic activation of the endothelium, which leads to atherosclerosis and cardiovascular disease (CVD). Intake of trans fatty acids (TFAs) is associated with an increased risk of CVD. This risk is usually associated with industrial TFAs (iTFAs) rather than ruminant TFAs (rTFAs); however it is not clear how specific TFA isomers differ in their biological activity and mechanisms of action with regard to inflammation. Here we review the literature on 18­carbon TFAs, including the research associating their intake or levels with CVD and studies relating 18­carbon TFA exposure to modulation of inflammatory processes. The evidence associating iTFAs with CVD risk factors is fairly consistent and studies in humans usually show a relation between iTFAs and higher levels of inflammatory markers. In contrast, studies in humans, animals and in vitro suggest that rTFAs have null or mildly beneficial effects in cardiovascular health, metabolic parameters and inflammatory markers, although the evidence is not always consistent. More studies are needed to better identify the beneficial and detrimental effects of the different TFAs, including those with 18 carbons.

Palmitoleic Acid has Stronger Anti-Inflammatory Potential in Human Endothelial Cells Compared to Oleic and Palmitic Acids.

SCOPE: Fatty acids (FAs) may affect endothelial cell (EC) function, influencing atherogenesis and inflammatory processes. Palmitoleic acid (POA) has been described as an anti-inflammatory FA. However, its effects on ECs are underexplored. This study compares the effects of POA with those of palmitic acid (PA) and oleic acid (OA) on EC inflammatory responses. METHODS AND RESULTS: EAHy926 cells (EC lineage) are exposed to PA, OA, or POA, and stimulated with tumor necrosis factor (TNF)-α. Associated with the FA's own incorporation, PA induces a twofold increase in arachidonic acid, while POA increases the amount of cis-vaccenic acid. PA, but not OA, enhances the production of IL-6 and IL-8 in response to TNF-α. In contrast, POA decreases production of monocyte chemotactic protein (MCP)-1, IL-6, and IL-8 compared to PA. TNF-α increases surface intercellular adhesion molecule-1 expression previously decreased by POA. TNF-α stimulation increases the expression of NFκB, cyclooxygenase (COX)-2, MCP-1, and IL-6 genes and reduces the expression of peroxisome proliferator-activated receptor (PPAR)-α gene. PA enhances the expression of MCP-1, IL-6, and COX-2 genes, while POA downregulates these genes, decreases expression of NFκB, and upregulates PPAR-α gene expression. CONCLUSION: POA has anti-inflammatory effects on ECs stimulated with TNF-α and may counter endothelial dysfunction.

Evidence for Involvement of IL-9 and IL-22 in Cows' Milk Allergy in Infants.

Although allergic inflammation is characterized by a T helper (Th) 2-dominant immune response, the discovery of a role for new T cell subsets in inflammatory diseases has added an additional layer of complexity to the understanding of the pathogeneses of allergic diseases. We evaluated plasma cytokine profiles in infants with cows' milk allergy (CMA), who were being treated with an elimination diet. In a prospective, randomized and controlled study, infants (aged 8.4 ± 3.9 months) with CMA were treated with an elimination diet for 120 days, which replaced cows' milk with a hydrolysed soy protein formula (n = 26) or a free amino acid formula (n = 20). Blood samples were collected before treatment during active disease (T0) and after 120 days, when symptoms were absent (T1). Plasma cytokine concentrations were measured. Infants with CMA had higher plasma concentrations of interleukin (IL)-4 and IL-13 and lower concentrations of IL-9, IL-17A and interferon-γ, compared with healthy breast-fed infants. At T0, there was a positive correlation between blood eosinophil numbers and plasma concentrations of IL-4, IL-9, IL-17A and IL-22. Treatment with a cows' milk elimination diet resulted in a decrease in plasma IL-4, IL-9, IL-13 and IL-22 and an increase in plasma IL-17A. We conclude that IL-4 and IL-13 are elevated in active CMA. The association of IL-9 and IL-22 with eosinophilia, and the decrease in these two cytokines with cows' milk elimination, suggests that they both play a role in the symptoms observed in CMA and may be important targets for future interventions.

Supplemental intravenous n-3 fatty acids and n-3 fatty acid status and outcome in critically ill elderly patients in the ICU receiving enteral nutrition.

BACKGROUND & AIMS: N-3 fatty acids (FA) may have benefits in ICU patients. The aims were to identify whether FA status is altered in critical illness and to evaluate the effect of supplemental intravenous n-3 FA on plasma FA status and clinical outcome in ICU patients receiving enteral nutrition. METHODS: Enterally fed patients (n = 49; 60-80 years) were recruited in the first 48 h of ICU admission. Fifteen patients received n-3 FA emulsion (0.2 g/kg) over 6 h for 3 consecutive days, and 34 patients did not (control). Samples were collected before supplementation, and 24 and 72 h after the third infusion. Nineteen healthy elderly subjects were also studied; they gave a single blood sample. FA were measured in plasma phosphatidylcholine (PC). RESULTS: Critically ill patients had altered plasma PC FA compared with healthy elderly subjects. Surviving ICU patients had higher levels of docosahexaenoic acid and total n-3 FA and a lower ratio of n-6:n-3 FA in plasma PC than non-survivors. Infusion of n-3 FA increased eicosapentaenoic, docosahexaenoic and total n-3 FA, and decreased arachidonic and total n-6 FA and n-6:n-3 FA and arachidonic:eicosapentaenoic acid ratios. Gas exchange was enhanced 72 h after the third n-3 FA infusion (p = 0.001). CONCLUSIONS: Critically ill patients may have altered plasma FA profiles. A higher total n-3 FA and docosahexaenoic acid content in plasma PC is associated with survival and improved gas exchange.

Fish oil n-3 polyunsaturated fatty acids selectively affect plasma cytokines and decrease illness in Thai schoolchildren: a randomized, double-blind, placebo-controlled intervention trial.

OBJECTIVE: To determine whether very long-chain n-3 polyunsaturated fatty acids (PUFAs) affect illness and selected plasma cytokines in schoolchildren. STUDY DESIGN: Thai schoolchildren aged 9 to 12 years consumed milk containing placebo (soybean) oil (n = 86) or fish oil (n = 94) on 5 days per week for 6 months; the latter provided 200 mg eicosapentaenoic acid plus 1 g docosahexaenoic acid daily. Episodes and duration of illness were recorded, and plasma interleukin (IL)-2 receptor, IL-6, IL-10, and transforming growth factor (TGF)-beta1 concentrations and the fatty acid profile of plasma phosphatidylcholine determined. RESULTS: After intervention, very long-chain n-3 PUFAs were higher in plasma phosphatidylcholine in the fish oil group than in the placebo group (P < .001). The fish oil group showed fewer episodes (P = .014) and shorter duration (P = .024) of illness (mainly upper respiratory tract) than the placebo group. Plasma IL-2 receptor, IL-10, and IL-6 were not affected by either treatment. Plasma TGF-beta1 increased in both groups, but the increase was smaller in the fish oil group, and at the end of supplementation TGF-beta1 concentration was lower in the fish oil group (P < .001). CONCLUSIONS: Very long-chain n-3 PUFAs reduce illness, mainly infections, in healthy Thai schoolchildren.

Differential effects of short-chain fatty acids on proliferation and production of pro- and anti-inflammatory cytokines by cultured lymphocytes.

Short-chain fatty acids (SCFA) are produced by fermentation of water-soluble fiber by anaerobic bacteria in the large bowel. Fiber-rich diets decrease the risk of developing inflammatory bowel disease (IBD) and butyrate enemas are effective as a therapy in some patients. Crohn's disease, one form of IBD, appears to involve an exagerated T helper-1 (Th1) lymphocyte phenotype, characterised by production of interleukin (IL)-2 and interferon (IFN)-gamma, that drives the inflammation. To examine whether SCFA influence pro- and anti-inflammatory cytokine production, rat mesenteric lymph node lymphocytes were cultured in the presence of acetate (10 mM), butyrate (1.5 mM) or propionate (2 mM) and the production of cytokines in response to concanavalin A determined. Butyrate, but not acetate or propionate, inhibited lymphocyte proliferation and IL-2 production. Acetate and propionate were able to partly prevent the inhibitory effect of butyrate on IL-2 production. Acetate and propionate increased IFN-gamma production, whereas butyrate inhibited it. Acetate and propionate in combination were able to prevent the inhibitory effect of butyrate on IFN-gamma production. IL-4 was not detected in any cultures. Acetate and propionate increased IL-10 production, which was not affected by butyrate. It is concluded that butyrate significantly inhibits Th1-type responses and that this might explain the therapeutic effect of butyrate in IBD patients. Acetate and propionate have less marked modulatory actions, and in some cases have effects that oppose those of butyrate. A combination of the three SCFA causes a shift in the T helper lymphocyte phenotype towards a more anti-inflammatory phenotype and this might explain the protective effects of fiber.