gamma-linolenic-acid and Inflammation

Inflammation is a normal process that is part of host defence and tissue healing. However, excessive or unresolved inflammation can lead to uncontrolled tissue damage, pathology and disease. In humans on a Western diet, the omega-6 polyunsaturated fatty acid arachidonic acid (ARA) makes a significant contribution to the fatty acids present in the membrane phospholipids of cells involved in inflammation. ARA is a precursor to a number of potent pro-inflammatory mediators including well described prostaglandins and leukotrienes, which has led to the development of anti-inflammatory pharmaceuticals that target the ARA pathway to successfully control inflammation. Hence, it is commonly believed that increasing dietary intake of the omega-6 fatty acids ARA or its precursor linoleic acid (LA) will increase inflammation. However, studies in healthy human adults have found that increased intake of ARA or LA does not increase the concentrations of many inflammatory markers. Epidemiological studies have even suggested that ARA and LA may be linked to reduced inflammation. Contrastingly, there is also evidence that a high omega-6 fatty acid diet inhibits the anti-inflammatory and inflammation-resolving effect of the omega-3 fatty acids. Thus, the interaction of omega-3 and omega-6 fatty acids and their lipid mediators in the context of inflammation is complex and still not properly understood.

Topics: Animals; Arachidonic Acid; Cytokines; Dietary Fats; Fatty Acids, Omega-3; Fatty Acids, Omega-6; gamma-Linolenic Acid; Humans; Inflammation; Leukocytes; Leukotrienes; Linoleic Acid; Lipid Metabolism; Lipoxins; Prostaglandins

Gamma-linolenic acid (GLA, 18:3n-6) is an omega-6 (n-6), 18 carbon (18C-) polyunsaturated fatty acid (PUFA) found in human milk and several botanical seed oils and is typically consumed as part of a dietary supplement. While there have been numerous in vitro and in vivo animal models which illustrate that GLA-supplemented diets attenuate inflammatory responses, clinical studies utilizing GLA or GLA in combination with omega-3 (n-3) PUFAs have been much less conclusive. A central premise of this review is that there are critical metabolic and genetic factors that affect the conversion of GLA to dihommo-gamma linolenic acid (DGLA, 20:3n-6) and arachidonic acid (AA, 20:4n-6), which consequently affects the balance of DGLA- and AA- derived metabolites. As a result, these factors impact the clinical effectiveness of GLA or GLA/(n-3) PUFA supplementations in treating inflammatory conditions. Specifically, these factors include: 1) the capacity for different human cells and tissues to convert GLA to DGLA and AA and to metabolize DGLA and AA to bioactive metabolites; 2) the opposing effects of DGLA and AA metabolites on inflammatory processes and diseases; and 3) the impact of genetic variations within the fatty acid desaturase (FADS) gene cluster, in particular, on AA/DGLA ratios and bioactive metabolites. We postulate that these factors influence the heterogeneity of results observed in GLA supplement-based clinical trials and suggest that "one-size fits all" approaches utilizing PUFA-based supplements may no longer be appropriate for the prevention and treatment of complex human diseases.

Topics: Animals; Dietary Supplements; Eicosanoids; gamma-Linolenic Acid; Humans; Inflammation; Multigene Family

Osteoarthritis (OA) is the most common cause of musculoskeletal disability in elderly individuals, and it places an enormous economic burden on society. Management of OA is primarily focused on palliative relief by using agents such as nonsteroidal anti-inflammatory drugs and analgesics. However, such an approach is limited by a narrow therapeutic focus that fails to address the progressive and multimodal nature of OA. Given the favorable safety profile of most nutritional interventions, identifying disease-modifying nutritional agents capable of improving symptoms and also preventing, slowing, or even reversing the degenerative process in OA should remain an important paradigm in translational and clinical research. Applying advances in nutritional science to musculoskeletal medicine remains challenging, given the fluid and dynamic nature of the field, along with a rapidly developing regulatory climate over manufacturing and commerce requirements. The aim of this article is to review the available literature on effectiveness and potential mechanism of macronutrients for OA, with a focus on the following: long-chain ω-3 essential fatty acids eicosapentaenoic acid and docosahexaenoic acid, functional ω-6 fatty acid γ-linolenic acid, and macronutrient composition of background diet. There also is a discussion about the concept of rational polysupplementation via the strategic integration of multiple nutraceuticals with potential complementary mechanisms for improving outcomes in OA. As applied nutritional science evolves, it will be important to stay on the forefront of proteomics, metabolomics, epigenetics, and nutrigenomics, because they hold enormous potential for developing novel therapeutic and prognostic breakthroughs in many areas of medicine, including OA.

Topics: Animals; Body Composition; Cartilage, Articular; Dietary Supplements; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fish Oils; gamma-Linolenic Acid; Humans; Inflammation; Lipids; Osteoarthritis; Weight Loss

Lipids traditionally used in artificial nutrition are based on n-6 fatty acid-rich vegetable oils like soyabean oil. This may not be optimal because it may present an excessive supply of linoleic acid. One alternative to the use of soyabean oil is its partial replacement by fish oil, which contains n-3 fatty acids. These fatty acids influence inflammatory and immune responses and so may be useful in particular situations where those responses are not optimal. Fish oil-containing lipid emulsions have been used in parenteral nutrition in adult patients post-surgery (mainly gastrointestinal). This has been associated with alterations in patterns of inflammatory mediators and in immune function and, in some studies, a reduction in length of intensive care unit (ICU) and hospital stay. Perioperative administration of fish oil may be superior to post-operative. Parenteral fish oil has been used in critically ill adults. Here the influence on inflammatory processes, immune function and clinical endpoints is not clear, since there are too few studies and those that are available report contradictory findings. Fish oil is included in combination with other nutrients in various enteral formulas. In post-surgical patients and in those with mild sepsis or trauma, there is clinical benefit from a formula including fish oil and arginine. A formula including fish oil, borage oil and antioxidants has demonstrated marked benefits on gas exchange, ventilation requirement, new organ failures, ICU stay and mortality in patients with acute respiratory distress syndrome, acute lung injury or severe sepsis.

Topics: Antioxidants; Critical Illness; Enteral Nutrition; Fatty Acids, Omega-3; gamma-Linolenic Acid; Humans; Inflammation; Parenteral Nutrition; Perioperative Care; Plant Oils

Changes in diet over the past century have markedly altered the consumption of fatty acids. The dramatic increase in the ingestion of saturated and n-6 fatty acids and concomitant decrease in n-3 fatty acids are thought to be a major driver of the increase in the incidence of inflammatory diseases such as asthma, allergy, and atherosclerosis. The central objective of the Center for Botanical Lipids at Wake Forest University School of Medicine and the Brigham and Women's Hospital is to delineate the mechanisms by which fatty acid-based dietary supplements inhibit inflammation leading to chronic human diseases such as cardiovascular disease and asthma. The key question that this center addresses is whether botanical n-6 and n-3 fatty acids directly block recognized biochemical pathways or the expression of critical genes that lead to asthma and atherosclerosis. Dietary supplementation with flaxseed oil, borage oil, and echium oil affects the biochemistry of fatty acid metabolism and thus the balance of proinflammatory mediators and atherogenic lipids. Supplementation studies have begun to identify key molecular and genetic mechanisms that regulate the production of lipid mediators involved in inflammatory and hyperlipidemic diseases. Echium oil and other oils containing stearidonic acid as well as botanical oil combinations (such as echium and borage oils) hold great promise for modulating inflammatory diseases.

Topics: Animals; Asthma; Atherosclerosis; Cholesterol; Chronic Disease; Dietary Fats; Dietary Fats, Unsaturated; Dietary Supplements; Echium; Fatty Acids, Omega-3; Fatty Acids, Omega-6; gamma-Linolenic Acid; Humans; Hyperlipidemias; Inflammation; Linseed Oil; Plant Oils; Signal Transduction; Triglycerides

Essential Fatty Acids (EFA), are unsaturated fatty acids not produced by human being, but essential for proper functioning of the human body. To EFA-s belongs: linoleic acid (LA) (18:2,cis detla(9,12), omega6)--precursor o f gamma-linolenic acid (GLA), gamma-linolenic acid (GLA) (18:3,cisA6,9,12, )6) and alpha-linolenic acid (ALA)(18:3,cisdelta(9, 12, 15), omega3)--product of dehydrogenation of linoleic acid (LA). Most important EFA is gamma-linolenic acid (GLA)--18 carbons, one-carboxylic, non-branched fatty acid with 3 double cis-bonds (the last is situated by 6-th carbon from methylic end). The diet devoided of EFA leads to decreased growth, skin and kidney injury and infertility. Modern research of GLA and others EFA's is concerned mainly on therapeutic impact on the inflammatory process. The biogenic amines, cytokines, prostaglandins, tromboxanes and leukotrienes are the main inflammatory mediators. The last three are described with the common name eicosanoides (eico-twenty). Eicosanoides are synthesized from 20-carbon unsaturated fatty acids: dihomo-gamma-linoleic (DGLA) (20:3, cis delta(8,11,14), omega6), arachidonic acid (AA-20:4, cis delta(5,8,11,14), omega6), and eicosapentaenoic acid (EPA-20:5, cis delta(5,8,11,14,17, omega3). Derivatives of gamma and gamma-linolenic acids regulate the inflammatory process, through their opposed activity. PG2, leucotrien C4 and tromboxan A2 have the strongest proinflammatory action. Derivatives of alpha-linolenic acid 15-HETE and prostaglandin E1 (PGE1) have weak pro-inflammatory action, or even anti-inflammatory (PGE1), and additionally, they inhibit the transformation of arachidonic acid (AA) to leukotriens. delta6-desaturase (transformes linolenic acid into gamma-linolenic acid by making additional double bond) is the slowest step of the fatty acid metabolism. It's activity is impaired by many physiological and pathologic factors and leads to gamma-linolenic acid (GLA) deficiency. The gamma-linolenic acid supplementation in diet allows to omitt the inefficient delta6-desaturase system which has an effect in rising of dihomo-gamma-linolenic acid (DGLA), arachidonic acid (AA) and their derivatives. This article describes biology of essential fatty acids and particularly the role of gamma-linolenic acid.

Topics: alpha-Linolenic Acid; Dietary Supplements; Eicosanoids; Fatty Acids, Essential; gamma-Linolenic Acid; Humans; Inflammation; Linoleic Acid

Inflammation plays an important role in health and disease. Most of the chronic diseases of modern society, including cancer, diabetes, heart disease, arthritis, Alzheimer's disease, etc. have inflammatory component. At the same time, the link between diet and disease is also being recognized. Amongst dietary constituents, fat has gained most recognition in affecting health. Saturated and trans fatty acids have been implicated in obesity, heart disease, diabetes and cancer while polyunsaturated fatty acids (PUFAs) generally have a positive effect on health. The PUFAs of omega-3 and omega-6 series play a significant role in health and disease by generating potent modulatory molecules for inflammatory responses, including eicosanoids (prostaglandins, and leukotrienes), and cytokines (interleukins) and affecting the gene expression of various bioactive molecules. Gamma linolenic acid (GLA, all cis 6, 9, 12-Octadecatrienoic acid, C18:3, n-6), is produced in the body from linoleic acid (all cis 6,9-octadecadienoic acid), an essential fatty acid of omega-6 series by the enzyme delta-6-desaturase. Preformed GLA is present in trace amounts in green leafy vegetables and in nuts. The most significant source of GLA for infants is breast milk. GLA is further metabolized to dihomogamma linlenic acid (DGLA) which undergoes oxidative metabolism by cyclooxygenases and lipoxygenases to produce anti-inflammatory eicosanoids (prostaglandins of series 1 and leukotrienes of series 3). GLA and its metabolites also affect expression of various genes where by regulating the levels of gene products including matrix proteins. These gene products play a significant role in immune functions and also in cell death (apoptosis). The present review will emphasize the role of GLA in modulating inflammatory response, and hence its potential applications as an anti-inflammatory nutrient or adjuvant.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Dietary Supplements; gamma-Linolenic Acid; Humans; Inflammation; Neoplasms

This review discusses the rationale and experimental data that led to clinical trials of certain botanical lipids, mainly gammalinolenic acid (GLA), for the treatment of rheumatoid arthritis (RA).. Pertinent articles and reviews, and a bibliographic database in English using the following indexing terms: rheumatoid arthritis, fatty acids, gammalinolenic acid, lymphocytes, and monocytes, were used.. All clinical trials in which GLA was used to treat arthritis are included in this review. Data from appropriately peer reviewed in vitro and animal experiments evaluating the effects of botanical lipids as regulators of cell activation and immune responses are also reviewed.. GLA treatment is associated with clinical improvement in patients with RA, as evaluated by duration of morning stiffness, joint pain and swelling, and ability to reduce other medications. However, studies vary in terms of duration, GLA dose, whether or not they were placebo controlled, and, if so, what placebo was used, criteria for evaluation, and use of concomitant medication. Studies done in vitro generally indicated that GLA reduces lymphocyte activation and production of mediators of inflammation.. A small number of studies suggest that GLA is effective treatment for RA patients. Further controlled studies of its use in RA seem warranted.

Topics: Animals; Arthritis, Rheumatoid; Blood Platelets; Clinical Trials as Topic; Eicosanoids; Fatty Acids; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; gamma-Linolenic Acid; Humans; Immune System; Inflammation; Lymphocytes; Phagocytes

The omega-3 (n-3) fatty acids docosahexaenoic acid and eicosapentaenoic acid, along with γ-linolenic acid and antioxidants, may modulate systemic inflammatory response and improve oxygenation and outcomes in patients with acute lung injury.. To determine if dietary supplementation of these substances to patients with acute lung injury would increase ventilator-free days to study day 28.. The OMEGA study, a randomized, double-blind, placebo-controlled, multicenter trial conducted from January 2, 2008, through February 21, 2009. Participants were 272 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition at 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. All participants had complete follow-up.. Twice-daily enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants compared with an isocaloric control. Enteral nutrition, directed by a protocol, was delivered separately from the study supplement.. Ventilator-free days to study day 28.. The study was stopped early for futility after 143 and 129 patients were enrolled in the n-3 and control groups. Despite an 8-fold increase in plasma eicosapentaenoic acid levels, patients receiving the n-3 supplement had fewer ventilator-free days (14.0 vs 17.2; P = .02) (difference, -3.2 [95% CI, -5.8 to -0.7]) and intensive care unit-free days (14.0 vs 16.7; P = .04). Patients in the n-3 group also had fewer nonpulmonary organ failure-free days (12.3 vs 15.5; P = .02). Sixty-day hospital mortality was 26.6% in the n-3 group vs 16.3% in the control group (P = .054), and adjusted 60-day mortality was 25.1% and 17.6% in the n-3 and control groups, respectively (P = .11). Use of the n-3 supplement resulted in more days with diarrhea (29% vs 21%; P = .001).. Twice-daily enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants did not improve the primary end point of ventilator-free days or other clinical outcomes in patients with acute lung injury and may be harmful.. clinicaltrials.gov Identifier: NCT00609180.

Topics: Acute Lung Injury; Adult; Aged; Antioxidants; Biomarkers; Dietary Supplements; Docosahexaenoic Acids; Double-Blind Method; Drug Therapy, Combination; Eicosapentaenoic Acid; Enteral Nutrition; Female; gamma-Linolenic Acid; Humans; Inflammation; Intensive Care Units; Male; Middle Aged; Pneumonia; Sepsis; Survival Analysis; Treatment Outcome; Ventilator Weaning

Chronic inflammation plays a major role in lung deterioration in cystic fibrosis (CF) patients and anti-inflammatory strategies have beneficial effects. To study the changes seen after a one-year course of low-dose dietary supplements with a mixture of fatty acids in adult patients with CF in chronic inflammation, pulmonary status (lung function, respiratory exacerbations and antibiotic consumption), quality of life and anthropometric parameters.. Seventeen adult subjects with CF received 324 mg of eicosapentaenoic, 216 mg of docosahexaenoic, 480 mg of linoleic and 258 mg of gammalinolenic acid daily. We assessed inflammation markers, spirometry parameters, number and severity of respiratory exacerbations, antibiotic consumption, quality of life (St George's QoL), anthropometric parameters and serum phospholipid fatty acid composition.. At the end of the treatment period TNF alpha levels fell significantly and its soluble receptors (60 and 80) rose significantly. Levels of IgG and IgM anti-oxidized LDL antibodies fell significantly. Spirometry improved significantly. Annual respiratory exacerbations and days of antibiotic treatment fell significantly. The improvement in QoL was not significant. Serum levels of docosahexaenoic, total omega-3 and linoleic acid rose significantly and more favourable profiles were seen in monoenoic acids, arachidonic acid and the arachidonic/docosahexaenoic ratio. The fat-free mass and hand grip dynamometry improved significantly.. Low-dose supplements of n-3 and gammalinolenic fatty acids over a long period (one year) appears to improve pulmonary status (lung function, respiratory exacerbations and antibiotic consumption), inflammatory and anthropometric parameters in adults with CF.

Topics: Adolescent; Adult; Anthropometry; Autoantibodies; Body Composition; Cystic Fibrosis; Dietary Supplements; Docosahexaenoic Acids; Eicosapentaenoic Acid; Female; gamma-Linolenic Acid; Humans; Inflammation; Linoleic Acid; Lipoproteins, LDL; Male; Quality of Life; Receptors, Tumor Necrosis Factor; Respiratory Function Tests; Respiratory Tract Infections; Severity of Illness Index; Sputum; Tumor Necrosis Factor-alpha; Vitamin E; Young Adult

Greatly increasing the amounts of flaxseed oil [rich in alpha-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, gamma-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-alpha, interleukin-1beta, 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.

Topics: Aged; alpha-Linolenic Acid; Arachidonic Acid; Cell Adhesion Molecules; Cytokines; Dietary Supplements; Docosahexaenoic Acids; Double-Blind Method; Eicosanoic Acids; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; gamma-Linolenic Acid; Humans; Inflammation; Male; Middle Aged; Neutrophils; Phagocytosis; Phospholipids; Respiratory Burst

Recent studies in animal models of sepsis-induced acute respiratory distress syndrome (ARDS) have shown that a low-carbohydrate, high-fat diet combining the anti-inflammatory and vasodilatory properties of eicosapentaenoic acid (EPA; fish oil), gamma-linolenic acid (GLA; borage oil) (EPA+GLA), and antioxidants improves lung microvascular permeability, oxygenation, and cardiopulmonary function and reduces proinflammatory eicosanoid synthesis and lung inflammation. These findings suggest that enteral nutrition with EPA+GLA and antioxidants may reduce pulmonary inflammation and may improve oxygenation and clinical outcomes in patients with ARDS.. Prospective, multicentered, double-blind, randomized controlled trial.. Intensive care units of five academic and teaching hospitals in the United States.. We enrolled 146 patients with ARDS (as defined by the American-European Consensus Conference) caused by sepsis/pneumonia, trauma, or aspiration injury in the study.. Patients meeting entry criteria were randomized and continuously tube-fed either EPA+GLA or an isonitrogenous, isocaloric standard diet at a minimum caloric delivery of 75% of basal energy expenditure x 1.3 for at least 4-7 days.. Arterial blood gases were measured, and ventilator settings were recorded at baseline and study days 4 and 7 to enable calculation of PaO2/FIO2, a measure of gas exchange. Pulmonary neutrophil recruitment was assessed by measuring the number of neutrophils and the total cell count in bronchoalveolar lavage fluid at the same time points. Clinical outcomes were recorded. Baseline characteristics of 98 evaluable patients revealed that key demographic, physiologic, and ventilatory variables were similar at entry between both groups. Multiple bronchoalveolar lavages revealed significant decreases (approximately 2.5-fold) in the number of total cells and neutrophils per mL of recovered lavage fluid during the study with EPA+GLA compared with patients fed the control diet. Significant improvements in oxygenation (PaO2/FIO2) from baseline to study days 4 and 7 with lower ventilation variables (FIO2, positive end-expiratory pressure, and minute ventilation) occurred in patients fed EPA+GLA compared with controls. Patients fed EPA+GLA required significantly fewer days of ventilatory support (11 vs. 16.3 days; p = .011), and had a decreased length of stay in the intensive care unit (12.8 vs. 17.5 days; p = .016) compared with controls. Only four of 51 (8%) patients fed EPA+GLA vs. 13 of 47 (28%) control patients developed a new organ failure during the study (p = .015).. The beneficial effects of the EPA+GLA diet on pulmonary neutrophil recruitment, gas exchange, requirement for mechanical ventilation, length of intensive care unit stay, and the reduction of new organ failures suggest that this enteral nutrition formula would be a useful adjuvant therapy in the clinical management of patients with or at risk of developing ARDS.

Topics: Antioxidants; Blood Gas Analysis; Bronchoalveolar Lavage Fluid; Double-Blind Method; Eicosapentaenoic Acid; Enteral Nutrition; Female; gamma-Linolenic Acid; Humans; Inflammation; Length of Stay; Leukocyte Count; Male; Middle Aged; Neutrophils; Prospective Studies; Pulmonary Gas Exchange; Pulmonary Ventilation; Respiration, Artificial; Respiratory Distress Syndrome

Atopic dermatitis (AD) is a chronic eczematous disease characterized by T helper 2 (Th2) -shifted allergic immunity, skin barrier impairment, and pruritus. Oral intake of certain nutrients might help regulate AD. Serum 25-hydroxyvitamin D levels are often low in patients with AD, and oral vitamin D supplementation improves AD. Vitamin D increases regulatory T (Treg) cells, which promote tolerance to allergens and prevent allergic inflammation by inducing expression of filaggrin and cathelicidin in keratinocytes. Vitamin A strengthens Treg cells by inducing expression of forkhead box P3 and inhibits mediator release from mast cells and eosinophils. Serum levels of γ-linolenic acid and its metabolite, dihomo-γ-linolenic acid, are low in patients with AD, and oral γ-linolenic acid improves AD through anti-inflammatory prostaglandin D

Topics: Bifidobacteriales Infections; Bifidobacterium; Dermatitis, Atopic; Filaggrin Proteins; gamma-Linolenic Acid; Humans; Inflammation; Lactobacillus; Nutritional Status; Probiotics; T-Lymphocytes, Regulatory; Treatment Outcome; Vitamin D; Zinc

Polycystic Ovary Syndrome (PCOS), a major endocrine disorder, affects the reproductive function of a woman, along with an association with metabolic conditions like insulin resistance and inflammation. The inflammatory nature of PCOS is much debated over, owing to numerous cases of elevation in cytokine levels. Studies have shown the beneficiary effect of Gamma-Linolenic acid (GLA) in reducing inflammation related to many conditions such as atopic dermatitis, rheumatoid arthritis, arterial disease, obesity, and even PCOS. The study aims at assessing the expression of inflammatory cytokines in the ovary and Peri-ovarian adipose tissue (POAT) of the Dehydroepiandrosterone (DHEA) induced PCOS rat model. Further, this study also evaluates the effect of γ-linolenic Acid (GLA) on these cytokines in POAT. Female Wistar rats were subcutaneously injected with 60 mg/kg DHEA daily for 28 days. These PCOS-induced rats were then orally administered with 50 mg/kg GLA for 14 days. The gene expression of cytokines was assessed by Real Time-PCR. The study showed an increase in the expression of cytokines in the ovary and POAT of the DHEA group. This suggests the role of ovarian adipose in adding to the pro-inflammatory state of PCOS. Moreover, the administration of GLA to the PCOS-induced rats resulted in a reduction of cytokine expression from the POAT, indicating that the compound was successful in reducing the associated inflammation. The study throws light on the possibility of using GLA as a supplementary or naturalistic alternative in ameliorating ovarian adipose-associated inflammation that accompanies PCOS.

Topics: Adipose Tissue; Animals; Cytokines; Disease Models, Animal; Female; gamma-Linolenic Acid; Humans; Inflammation; Ovary; Polycystic Ovary Syndrome; Rats

The inflammatory responses associated with polycystic ovary syndrome (PCOS) may play a significant role in the severity of the disease. Emerging evidence report states that the polyunsaturated fatty acids are capable of ameliorating the PCOS condition. The therapeutic effects of γ-linolenic acid (GLA), an omega-6 fatty acid, in various inflammatory diseases have been reported. Yet, its role in PCOS associated inflammatory response remains unexplored. The aim of the study was to decipher the effects of GLA in PCOS and its role in the PPAR-γ pathway. In our study, female Wistar rats were stimulated with daily subcutaneous injections of DHEA (60 mg/kg per day) for 28 days to induce PCOS. Daily doses of GLA(10, 20, and 50 mg/kg) and Pioglitazone (P)(30 mg/kg) were administered orally for 14 days after PCOS induction. The levels of DHEA, leptin, PPAR-γ were measured by ELISA. The gene expression levels of leptin, TNF-α, IL-33, PPAR-γ, C/EBP-β, SREBP-1were determined by Real Time-PCR. We observed that the GLA significantly attenuated the DHEA and leptin levels. GLA treatment also upregulated PPAR-γ expression, when compared to the DHEA group. Further, GLA treatment showed a significant reduction in DHEA induced TNF-α, IL-33, C/EBP-β, and SREBP-1 levels in Wistar rat polycystic ovary tissue samples. The present findings could indicate that GLA is able to reduce the inflammatory response due to DHEA stimulation and thereafter potentially attenuate PCOS via the PPAR-γ pathway.

Topics: Animals; Dehydroepiandrosterone; Female; gamma-Linolenic Acid; Gene Expression; Inflammation; Peroxidase; Polycystic Ovary Syndrome; PPAR gamma; Rats; Rats, Wistar; Signal Transduction

Gamma-linolenic acid (GLA) and linoleic acid (LA), which are both n-6 unsaturated fatty acids, play vital roles in lipopolysaccharide (LPS)-induced inflammation. The multi-functional protein scavenger receptor CD36 has also been shown to participate in inflammation. However, the molecular mechanisms underlying the interactions between CD36 and GLA or LA in LPS-induced inflammation remain unclear. We used small interfering RNA and adenoviral systems to manipulate CD36 expression in primary goat mammary gland epithelial cells (pGMECs), and the results showed that nuclear factor kappa B (NF-κB) levels were significantly decreased by CD36 receptor signaling following treatment with GLA but not LA. GLA inhibited NF-κB activation in LPS-induced pGMECs. However, silencing CD36 or deleting its fatty acid-binding domain blocked the anti-inflammatory effects of GLA, resulting in an increase in NF-κB activation and disrupting its localization during LPS-induced inflammation. The activity of the cytokines IL-1β, IL-6, and TNF-α, which act downstream of NF-κB, was also modulated when CD34 expression was manipulated by the addition of GLA in LPS-induced pGMECs. Our data suggest that GLA, but not LA, may interact with the CD36 fatty acid-binding domain to regulate the activation and localization of NF-κB in LPS-induced pGMECs.

Topics: alpha-Linolenic Acid; Animals; CD36 Antigens; Cells, Cultured; Cytokines; Epithelial Cells; Female; gamma-Linolenic Acid; Goats; Inflammation; Lipopolysaccharides; Mammary Glands, Animal; NF-kappa B; RNA, Small Interfering; Signal Transduction

Fibrosis is induced by the excessive and abnormal deposition of extracellular matrix (ECM) with various growth factors in tissues. Transforming growth factor beta 1 (TGF-β1), plays a role in inducing apoptosis, modulates fibrosis, and ECM accumulation. Plasminogen activator inhibitor 1 (PAI-1) plays an important role in the development hepatic fibrosis. The overexpression of PAI-1 induces ECM accumulation, the main hallmark of chronic liver diseases. Death of hepatocytes is a characteristic feature of chronic liver disease due to various causes. The TGF-β1-mediated apoptotic pathway is regarded as a promising therapeutic target in hepatic fibrosis. Gamma-linolenic acid (GLA) is of special interest as it possesses anti-fibrosis, anti-inflammatory, and anti-cancer properties. However, the precise mechanism for GLA in chronic liver disease is not still clear. The aim of the present study was to determine whether GLA prevents hepatic PAI-1 expression and apoptosis through the inhibition of TGF-β1-mediated molecular mediators. GLA attenuated TGF-β1-stimulated PAI-1 expression, and inhibited PAI-1 promoter activity in AML12 cells. This effect was mediated by Smad3/4, the p38 pathways. We also found that GLA suppressed TGF-β1-induced apoptotic activation of the Bcl-2 family and caspase family of proteins, which resulted in the inhibition of poly-ADP-ribose polymerase 1 cleavage. GLA ameliorates the pro-fibrotic and pro-apoptotic effects of TGF-β1 in hepatocytes, suggesting GLA exerts a protective effect on hepatocytes and has a therapeutic potential for the treatment of chronic liver disease.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Cell Line; Fibrosis; gamma-Linolenic Acid; Gene Expression Regulation; Hepatocytes; Inflammation; Mice; Mitochondria; p38 Mitogen-Activated Protein Kinases; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Promoter Regions, Genetic; Protein Binding; Proto-Oncogene Proteins c-bcl-2; Serpin E2; Signal Transduction; Smad3 Protein; Smad4 Protein; Transforming Growth Factor beta1

Evening primrose (Oenothera biennis L., Onagraceae) is a wild medicinal plant of Central American origin that is now one of the most widely used herbal medicines in different parts of the world. Oil extracted from it seeds is traditionally used in the treatment of eczema, asthma, rheumatoid arthritis, breast problem, premenstrual and menopausal syndrome, all they have an inflammatory component. The present study demonstrates the in vitro anti-inflammatory effect of long-chain fatty alcohols, minor compounds isolated from Evening primrose oil (EPO).. A mixture of long chain fatty alcohols (LCFAs) was isolated from the non-triacylglycerol fraction of the EPO. Hexacosanol (C26OH: 38.65%), tetracosanol (C24OH: 31.59%), docosanol (C22OH: 11.36%) and octocosanol (C28OH: 7.64%), were the major constituents, identified and quantified by GC and GC-MS. LCFA was tested with LPS stimulated murine peritoneal macrophage. This fraction, significantly and dose-dependently decreased nitric oxide production induced by LPS (P<0.001) and the inhibitory effect seems to be consequence of an action at the level of the inducible nitric-oxide synthethase (iNOS) gene enzyme expression rather than to a direct inhibitory action on enzyme activity. The release of PLA2 and TXB2 also was significantly inhibited by LCFAs (P<0.001) although LCFAs did not affect to PGE2 generation, however the western blot assay showed that LCFAs reduced cyclooxygenase-2 enzyme gene expression at all doses assayed. In the same way, the secretion of inflammatory cytokines interleukin 1β (IL-1β) and tumour necrosis factor α (TNF-α) from LPS-stimulated murine macrophage, were also significantly reduced (P<0.001).. These results demonstrates the anti-inflammatory activity of LCFAs, providing an additional value about the role of bioactive minor compounds in the beneficial effect of EPO and supports its traditional uses in inflammatory processes management.

Topics: Animals; Cell Survival; Dinoprostone; Fatty Alcohols; gamma-Linolenic Acid; Gene Expression Regulation; Inflammation; Interleukin-1beta; Linoleic Acids; Macrophages, Peritoneal; Mice; Nitrites; Oenothera biennis; Phospholipases A2, Secretory; Plant Oils; Thromboxane B2; Tumor Necrosis Factor-alpha

Rheumatoid arthritis is a chronic inflammatory disease characterized by overproduction of inflammatory mediators along with undermined oxidative defensive mechanisms. Pathological angiogenesis was found to play a critical role in the progression of this disease. The current study was carried out to evaluate the anti-angiogenic, anti-inflammatory, and anti-oxidant effects of evening primrose oil (EPO), rich in gamma linolenic acid (GLA), either alone or in combination with aspirin or celecoxib, on adjuvant-induced arthritis. Arthritis was induced by subcutaneous injection of complete Freund's adjuvant (CFA) in the right hind paw of male albino rats. All treatments were administered orally from day 0 (EPO, 5 g/kg b.w.) or day 4 (celecoxib, 5 mg/kg; aspirin, 150 mg/kg) till day 27 after CFA injection. In the arthritic group, the results revealed significant decrease in the body weight and increase in ankle circumference, plasma angiopoietin-1 (ANG-1) and tumor necrosis factor-alpha (TNF-α) levels. Anti-oxidant status was suppressed as manifested by significant decline in reduced glutathione content along with decreased enzymatic activity of superoxide dismutase and increased lipid peroxidation. Oral administration of EPO exerted normalization of body weight, ANG-1, and TNF-α levels with restoration of activity as shown by reduced malondialdehyde levels. Moreover, histopathological examination demonstrated that EPO significantly reduced the synovial hyperplasia and inflammatory cells invasion in joint tissues, an effect that was enhanced by combination with aspirin or celecoxib. The joint use of GLA-rich natural oils, which possess anti-angiogenic, anti-inflammatory, and anti-oxidant activities, with traditional analgesics represents a promising strategy to restrain the progression of rheumatoid arthritis.

Topics: Administration, Oral; Angiopoietin-1; Animals; Anti-Inflammatory Agents; Antioxidants; Arthritis, Experimental; Arthritis, Rheumatoid; Aspirin; Celecoxib; Disease Progression; Drug Therapy, Combination; gamma-Linolenic Acid; Inflammation; Linoleic Acids; Lipid Peroxidation; Male; Neovascularization, Pathologic; Oenothera biennis; Oxidative Stress; Plant Oils; Pyrazoles; Rats; Rats, Wistar; Sulfonamides; Tumor Necrosis Factor-alpha

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an independent risk factor for CVD and has been proposed as a marker of vascular inflammation. Polyunsaturated n-3 fatty acids (FA) and several n-6 FA are known to suppress inflammation and may influence Lp-PLA2 mass and activity. The associations of n-3 and n-6 plasma FA with Lp-PLA2 mass and activity were analysed using linear regression analysis in 2246 participants of the Multi-Ethnic Study of Atherosclerosis; statistical adjustments were made to control for body mass, inflammation, lipids, diabetes, and additional clinical and demographic factors. Lp-PLA2 mass and activity were significantly lower in participants with the higher n-3 FA EPA (β = - 4·72, P< 0·001; β = - 1·53; P= 0·023) and DHA levels (β = - 4·47, β = - 1·87; both P< 0·001). Those in the highest quintiles of plasma EPA and DHA showed 12·71 and 19·15 ng/ml lower Lp-PLA2 mass and 5·7 and 8·90 nmol/min per ml lower Lp-PLA2 activity than those in the first quintiles, respectively. In addition, lower Lp-PLA2 mass and activity were associated with higher levels of n-6 arachidonic acid (β = - 1·63, β = - 1·30; both P< 0·001), while γ-linolenic acid was negatively associated with activity (β = - 27·7, P= 0·027). Lp-PLA2 mass was significantly higher in participants with greater plasma levels of n-6 linoleic (β = 0·828, P= 0·011) and dihomo-γ-linolenic acids (β = 4·17, P= 0·002). Based on their independent associations with Lp-PLA2 mass and activity, certain n-3 and n-6 FA may have additional influences on CVD risk. Intervention studies are warranted to assess whether these macronutrients may directly influence Lp-PLA2 expression or activity.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Aged; Atherosclerosis; Docosahexaenoic Acids; Eicosapentaenoic Acid; Female; gamma-Linolenic Acid; Humans; Inflammation; Linoleic Acid; Male; Middle Aged; Regression Analysis; Risk Factors

Dietary supplementation with botanical oils that contain n-6 and n-3 eighteen carbon chain (18C)-PUFA such as γ linolenic acid (GLA, 18:3n-6), stearidonic acid (SDA, 18:4n-3) and α linolenic acid (ALA, 18:3n-3) have been shown to impact PUFA metabolism, alter inflammatory processes including arachidonic acid (AA) metabolism and improve inflammatory disorders.. The diet of mild asthmatics patients was supplemented for three weeks with varying doses of two botanical seed oils (borage oil [Borago officinalis, BO] and echium seed oil [Echium plantagineum; EO]) that contain SDA, ALA and GLA. A three week wash out period followed. The impact of these dietary manipulations was evaluated for several biochemical endpoints, including in vivo PUFA metabolism and ex vivo leukotriene generation from stimulated leukocytes.. Supplementation with several EO/BO combinations increased circulating 20-22 carbon (20-22C) PUFAs, including eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and dihommo-gammalinolenic acid (DGLA), which have been shown to inhibit AA metabolism and inflammation without impacting circulating AA levels. BO/EO combinations also inhibited ex vivo leukotriene generation with some combinations attenuating cysteinyl leukotriene generation in stimulated basophils by >50% and in stimulated neutrophils by >35%.. This study shows that dietary supplementation with BO/EO alters 20-22C PUFA levels and attenuates leukotriene production in a manner consistent with a reduction in inflammation.

Topics: 8,11,14-Eicosatrienoic Acid; Adolescent; Adult; alpha-Linolenic Acid; Asthma; Cells, Cultured; Dietary Supplements; Echium; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Female; gamma-Linolenic Acid; Humans; Inflammation; Leukocytes, Mononuclear; Leukotrienes; Male; Middle Aged; Plant Oils; Seeds

This protocol describes microsphere-based protease assays for use in flow cytometry and high-throughput screening. This platform measures a loss of fluorescence from the surface of a microsphere due to the cleavage of an attached fluorescent protease substrate by a suitable protease enzyme. The assay format can be adapted to any site or protein-specific protease of interest and results can be measured in both real time and as endpoint fluorescence assays on a flow cytometer. Endpoint assays are easily adapted to microplate format for flow cytometry high-throughput analysis and inhibitor screening.

Topics: Animals; Biotinylation; Flow Cytometry; Fluorescence Resonance Energy Transfer; Green Fluorescent Proteins; High-Throughput Screening Assays; Humans; Inflammation; Kinetics; Microspheres; Peptide Hydrolases; Peptides; Reproducibility of Results; Temperature

Gamma linolenic acid (GLA) is a member of the n-6 family of polyunsaturated fatty acids and can be synthesized from linoleic acid (LA) by the enzyme delta-6-desaturase. The therapeutic values of GLA supplementation have been documented, but the molecular mechanism behind the action of GLA in health benefits is not clear. In this study, we assessed the effect of GLA with that of LA on lipopolysaccharide (LPS)-induced inflammatory responses and further explored the molecular mechanism underlying the pharmacological properties of GLA in mouse RAW 264.7 macrophages. GLA significantly inhibited LPS-induced protein expression of inducible nitric oxide synthase, pro-interleukin-1beta, and cyclooxygenase-2 as well as nitric oxide production and the intracellular glutathione level. LA was less potent than GLA in inhibiting LPS-induced inflammatory mediators. Both GLA and LA treatments dramatically inhibited LPS-induced IkappaB-alpha degradation, IkappaB-alpha phosphorylation, and nuclear p65 protein expression. Moreover, LPS-induced nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) nuclear protein-DNA binding affinity and reporter gene activity were significantly decreased by LA and GLA. Exogenous addition of GLA but not LA significantly reduced LPS-induced expression of phosphorylated extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK)-1. Our data suggest that GLA inhibits inflammatory responses through inactivation of NF-kappaB and AP-1 by suppressed oxidative stress and signal transduction pathway of ERK and JNK in LPS-induced RAW 264.7 macrophages.

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Cell Survival; Cyclooxygenase 2; Dose-Response Relationship, Drug; gamma-Linolenic Acid; Glutathione; I-kappa B Kinase; Inflammation; Interleukin-1; Lipopolysaccharides; Macrophages; Mice; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinase 8; Nitric Oxide; Nitric Oxide Synthase Type II; Phosphorylation; Protein Precursors; RNA, Messenger; Signal Transduction; Transcription Factor AP-1; Transcription Factor RelA

Over the past 100 years, changes in the food supply in Western nations have resulted in alterations in dietary fatty acid consumption, leading to a dramatic increase in the ratio of omega-6 (omega6) to omega3 polyunsaturated fatty acids (PUFA) in circulation and in tissues. Increased omega6/omega3 ratios are hypothesized to increase inflammatory mediator production, leading to higher incidence of inflammatory diseases, and may impact inflammatory gene expression. To determine the effect of reducing the omega6/omega3 ratio on expression of inflammatory pathway genes in mononuclear cells, healthy humans were placed on a controlled diet for 1 week, then given fish oil and borage oil for an additional 4 weeks. Serum and neutrophil fatty acid composition and ex vivo leukotriene B(4) production from stimulated neutrophils were measured at the start and end of the supplementation period and after a 2-week washout. RNA was isolated from mononuclear cells and expression of PI3K, Akt, NFkappaB, and inflammatory cytokines was measured by real-time PCR. A marked increase was seen in serum and neutrophil levels of long-chain omega3 PUFA concomitant with a reduction in the omega6/omega3 PUFA ratio (40%). The ex vivo capacity of stimulated neutrophils to produce leukotriene B(4) was decreased by 31%. Expression of PI3Kalpha and PI3Kgamma and the quantity of PI3Kalpha protein in mononuclear cells was reduced after supplementation, as was the expression of several proinflammatory cytokines. These data reveal that PUFA may exert their clinical effects via their capacity to regulate the expression of signal transduction genes and genes for proinflammatory cytokines.

Topics: Dietary Fats; Dietary Fats, Unsaturated; Fatty Acids; Fatty Acids, Omega-3; Fish Oils; gamma-Linolenic Acid; Gene Expression Regulation; Humans; Inflammation; Kinetics; Leukocytes, Mononuclear; Leukotriene B4; Neutrophils; Phosphatidylinositol 3-Kinases; Plant Oils; Reverse Transcriptase Polymerase Chain Reaction; RNA

Virgin olive oil (VOO) compared with fish oil (FO) and evening primrose oil (PO) on the ability of stimulated leukocytes to produce inflammatory mediators was investigated in rats. Weaned Wistar rats were fed a basal diet (BD) (2% by weight of corn oil) or diets containing 15% by weight of VOO, PO, or FO. After 8 weeks, glycogen-elicited peritoneal polymorphonuclear leukocytes, mainly neutrophils, were isolated. The calcium-ionophore stimulated neutrophils (2.5 x 10(6) cells/mL) obtained from rats fed the different oils produced a higher release of lysosomal enzymes (beta-glucuronidase, lysozyme, and myeloperoxidase [MPO]) compared with those fed BD. The production of reactive oxygen species (ROS) in response to the stimulant, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), by neutrophils from the VOO group (15.44 nmol of O(2)(-) and 6.56 nmol of H(2)O(2)) was similar to the BD group (12.01 nmol O(2)(-) and 8.49 nmol H(2)O(2)) and significantly lower than the PO (20.90 nmol O(2)(-) and 10.84 nmol H(2)O(2)) and FO (20.93 nmol O(2)(-) and 12.79 nmol H(2)O(2)) groups. The cyclooxygenase-derived eicosanoid production was reduced by the lipid enrichment of the diets. Whereas the generation of prostaglandin E(2) (PGE(2)) was significantly decreased in VOO (5.40 ng/mL), PO (4.95 ng/mL), and FO (1.44 ng/mL) groups compared with BD (8.19 ng/mL), thromboxane B(2) (TXB(2)) reduction was especially significant in neutrophils from the FO diet group (14.67 ng/mL compared with 26.69 ng/mL from BD). These experimental data suggest that FO and PO, as well as VOO, could be considered a valuable strategy in preventing the generation of some inflammatory mediators.

Topics: Animals; Arachidonic Acid; Calcimycin; Dietary Fats, Unsaturated; Dinoprostone; Eicosanoids; Fatty Acids; Fatty Acids, Essential; Fish Oils; gamma-Linolenic Acid; Glucuronidase; Glycogen; Hydrogen Peroxide; Inflammation; Linoleic Acid; Linoleic Acids; Lysosomes; Male; Muramidase; Neutrophils; Oenothera biennis; Oleic Acid; Olive Oil; Peritoneum; Peroxidase; Plant Oils; Rats; Rats, Wistar; Reactive Oxygen Species; Superoxides; Tetradecanoylphorbol Acetate; Thromboxane B2

Inflammatory changes in brain exert a negative impact on cognitive function and in animal studies, these changes are associated with impairment in hippocampal-dependent learning paradigms and in long-term potentiation (LTP), which is a putative biological substrate for learning and/or memory. Lipopolysaccharide (LPS), a component of the cell wall of gram negative bacteria, induces inflammatory changes in the brain and leads to impairment of LTP. Since eicosapentaenoic acid (EPA) inhibits LPS-induced changes in vitro, we assessed the possibility that treatment of rats with EPA, alone or in combination with gamma-linolenic acid (GLA) might inhibit LPS-induced changes in vivo. The data presented indicate that the LPS-induced inhibition of LTP and decrease in hippocampal concentration of anti-inflammatory cytokines IL-10 and IL-4 are blocked in rats treated with EPA, GLA or both. The evidence suggests that these effects may be coupled with fatty acid-induced up-regulation of peroxisome proliferator-activated receptor-gamma which possesses known anti-inflammatory effects.

Topics: Animals; Eicosapentaenoic Acid; gamma-Linolenic Acid; Hippocampus; Inflammation; Injections, Intraperitoneal; Interleukin-10; Interleukin-4; Lipopolysaccharides; Long-Term Potentiation; Male; PPAR gamma; Rats; Rats, Wistar; Up-Regulation

The present study demonstrated that an omega (n)-3 fatty acid, ethyl-eicosapentaenoic acid (ethyl-EPA), supplemented diet significantly attenuated the stress/anxiety behavior of rats in the "open field" and elevated plus maze, which was induced by subchronic intracerebroventricular administration of proinflammatory cytokine interleukin (IL)-1beta. Ethyl-EPA also reduced the rise in serum corticosterone induced by IL-1. The n-6 fatty acid ethyl-gamma-linolenic acid (ethyl-GLA) had little effect on the IL-1-induced changes in behavior and the corticosterone concentration. Following IL-1beta administration, ethyl-EPA reduced the elevated prostaglandin (PG) E2 secretion and increased the secretion of antiinflammatory cytokine IL-10 from whole blood cells. Ethyl-GLA showed a similar antiinflammatory effect to ethyl-EPA. By contrast, n-6 fatty acid arachidonic acid (AA) had no effect on the behavior, immune, and endocrine changes induced by IL-1. AA alone enhanced the basal inflammatory response, raised serum corticosterone concentrations, and induced anxiety behavior in the elevated plus maze. The reduced growth rates of rats following the administration of IL-1 was attenuated by ethyl-EPA, and to a greater extent by ethyl-EPA plus ethyl-GLA, but not by AA alone or in combination with ethyl-EPA. Thus, ethyl-EPA would appear to antagonise the endocrine, immune, and behavioral effects of subchronic IL-1 administration. Ethyl-GLA only antagonised IL-1-induced inflammatory changes, whereas AA caused an increase in the secretion of corticosterone and PGE2, and induced anxiety-like behavior without enhancing the effects of IL-1.

Topics: Animals; Anxiety; Arachidonic Acid; Corticosterone; Diet; Dinoprostone; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Omega-6; gamma-Linolenic Acid; Inflammation; Interleukin-1; Interleukin-10; Phospholipids; Rats; Rats, Wistar; Stimulation, Chemical; Stress, Physiological

The subcutaneous air pouch formed in Sprague-Dawley rats was used to study the effect of diets enriched in black currant seed oil (BCSO) on acute inflammation induced by monosodium urate crystals. The BCSO enriched diet suppressed significantly both the cellular and fluid phases of inflammation (polymorphonuclear leucocyte and exudate accumulation). In contrast, administration of normal chow or of a diet enriched in safflower oil (polyunsaturated fatty acid control) did not influence monosodium urate crystal-induced inflammation in this model. The findings indicate that a diet which provides both n-6 (gammalinolenic acid) and n-3 (alpha-linolenic acid) fatty acids as substrates alternative to arachidonatic acid for oxidative metabolism, modifies monosodium urate crystal-induced acute inflammation.

Topics: Administration, Oral; Animals; Body Weight; Diet; Female; gamma-Linolenic Acid; Inflammation; Leukocyte Count; Male; Neutrophils; Plant Oils; Rats; Rats, Sprague-Dawley; Safflower Oil; Uric Acid

We examined the effect of diets enriched in gamma linolenic acid (GLA) on acute inflammation induced by monosodium urate crystals, and on subacute and chronic inflammation induced by complete Freund's adjuvant in the rat subcutaneous air pouch and in rats with adjuvant induced arthritis. Diets were enriched (15% fat) with borage seed oil (23% GLA) or safflower oil (less than 1% GLA). Diets enriched with GLA suppressed inflammation markedly in all models, whereas the safflower oil diet did not influence the inflammatory response. The degree of inflammation was quantified by measuring pouch exudate cell concentration, lysosomal enzyme activity, volume, protein concentration and prostaglandin E2 and leukotriene B4 concentrations. In the chronic air pouch model, the pouch lining was thickened, invaded by mononuclear cells and exhibited proliferation of lining cells 14 days after adjuvant injection. The lesion was far less severe and usual pouch lining architecture was maintained in animals given dietary GLA. Livers of rats fed borage seed oil were enriched in GLA and dihomo gamma linolenic acid (DGLA), and the DGLA/arachidonate ratio was increased 5-fold compared with animals fed safflower oil. Enrichment of diet with plant seed oils rich in GLA may provide a way to alter generation of prostaglandins and leukotrienes and to influence acute and chronic inflammatory responses.

Topics: Acute-Phase Reaction; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Chronic Disease; Diet; Eicosanoic Acids; gamma-Linolenic Acid; Inflammation; Linolenic Acids; Rats; Uric Acid

A subcutaneous air pouch formed in Sprague-Dawley rats was used to study the effect of diets enriched in gamma-linolenic acid (GLA) (in plant seed oil) and eicosapentaenoic acid (EPA) (in fish oil) on acute inflammation induced by monosodium urate crystals. The GLA-enriched diet suppressed significantly the cellular phase of inflammation (polymorphonuclear leukocyte accumulation, crystal phagocytosis, and lysosomal enzyme activity), but it had little effect on the fluid phase (exudate volume and protein concentration). In contrast, the EPA-enriched diet suppressed the fluid phase but not the cellular phase of inflammation. The findings indicate that the fluid and cellular phases of acute inflammation can be controlled independently. A combined diet of fish oil and plant seed oil (EPA-enriched and GLA-enriched) reduced both the cellular and fluid phases of inflammation. Thus, dietary provision of alternative substrates for oxidative metabolism (other than arachidonic acid) modifies monosodium urate crystal-induced acute inflammation.

Topics: Animals; Dietary Fats, Unsaturated; Dinoprostone; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Essential; Female; Fish Oils; gamma-Linolenic Acid; Inflammation; Linoleic Acids; Linolenic Acids; Male; Oenothera biennis; Phagocytosis; Plant Oils; Rats; Rats, Inbred Strains; Uric Acid

Topics: Animals; Arthritis; Arthritis, Experimental; Chronic Disease; Dermatologic Agents; Dietary Fats; Fatty Acids, Essential; Fatty Acids, Unsaturated; gamma-Linolenic Acid; Humans; Immunity, Cellular; Inflammation; Linoleic Acids; Oenothera biennis; Plant Oils