linoleic-acid and Hypersensitivity

Patients with atopic eczema and a mixture of allergic illnesses show biochemical evidence suggesting impairment in the desaturation of linoleic acid and linolenic acid by the enzyme delta-6 dehydrogenase. Consequences of this enzyme defect are 1) diminished synthesis of the 20-carbon polyunsaturated fatty acids, which are prostaglandin precursors and 2) a reduction in the concentration of double bonds in the cell membrane. A distortion in the production of prostaglandins and leukotrienes, which might result from this block, can account for the immunological defects of atopy and a variety of clinical symptoms experienced by atopic individuals. Dietary supplementation with essential fatty acids relieves the signs and symptoms of atopic eczema, may improve other types of allergic inflammation, and may also correct coexisting symptoms as diverse as excessive thirst and dysmenorrhea. Further research is suggested to test the hypothesis that some atopic states represent a condition of essential fatty acid dependency owing to defective desaturation of dietary fatty acids.

Topics: Adult; alpha-Linolenic Acid; Cardiac Complexes, Premature; Child; Delta-5 Fatty Acid Desaturase; Dietary Fats; Eczema; Encopresis; Enuresis; Fatty Acid Desaturases; Fatty Acids, Essential; Fatty Acids, Unsaturated; Female; Food, Fortified; gamma-Linolenic Acid; Humans; Hypersensitivity; Linoleic Acid; Linoleic Acids; Linolenic Acids; Linoleoyl-CoA Desaturase; Linseed Oil; Male; Middle Aged; Oenothera biennis; Plant Oils; Prostaglandins; Thirst

Studies have highlighted the role of nutritional and metabolic modulators in asthma pathobiology. Steroid resistance is an important clinical problem in asthma but lacks good experimental models. Linoleic acid, a polyunsaturated fatty acid, has been linked to asthma and glucocorticoid sensitivity. Its 12/15-lipoxygenase metabolite, 13-S-hydroxyoctadecadienoic acid (HODE) induces mitochondrial dysfunction, with severe airway obstruction and neutrophilic airway inflammation. Here we show that HODE administration leads to steroid unresponsiveness in an otherwise steroid responsive model of allergic airway inflammation (AAI). HODE treatment to allergic mice further increased airway hyperresponsiveness and goblet metaplasia. Treatment with dexamethasone was associated with increased neutrophilic inflammation in HODE treated allergic mice; unlike control allergic mice that showed resolution of inflammation. HODE induced loss of steroid sensitivity was associated with increased p-NFkB in mice and reduced GR-α transcript levels in cultured human bronchial epithelia. In summary, HODE modifies typical AAI to recapitulate many of the phenotypic features seen in severe steroid unresponsive asthma. We speculate that since HODE is a natural metabolite, it may be relevant to the increased asthma severity and steroid insensitivity in patients who are obese or consume high fat diets. Further characterization of HODE induced steroid insensitivity may clarify the mechanisms.

Topics: Animals; Anti-Asthmatic Agents; Asthma; Disease Models, Animal; Drug Resistance; Epithelial Cells; Humans; Hypersensitivity; Linoleic Acid; Lipid Metabolism; Mice; NF-kappa B; Receptors, Glucocorticoid; Respiratory Mucosa; Steroids

Oxylipins are oxidised fatty acids that can exert lipid mediator functions in inflammation, and several oxylipins derived from arachidonic acid are linked to asthma. This study quantified oxylipin profiles in different regions of the lung to obtain a broad-scale characterisation of the allergic asthmatic inflammation in relation to healthy individuals. Bronchoalveolar lavage fluid (BALF), bronchial wash fluid and endobronchial mucosal biopsies were collected from 16 healthy and 16 mildly allergic asthmatic individuals. Inflammatory cell counts, immunohistochemical staining and oxylipin profiling were performed. Univariate and multivariate statistics were employed to evaluate compartment-dependent and diagnosis-dependent oxylipin profiles in relation to other measured parameters. Multivariate modelling showed significantly different bronchial wash fluid and BALF oxylipin profiles in both groups (R(2)Y[cum]=0.822 and Q(2)[cum]=0.759). Total oxylipin concentrations and five individual oxylipins, primarily from the lipoxygenase (LOX) pathway of arachidonic and linoleic acid, were elevated in bronchial wash fluid from asthmatics compared to that from healthy controls, supported by immunohistochemical staining of 15-LOX-1 in the bronchial epithelium. No difference between the groups was found among BALF oxylipins. In conclusion, bronchial wash fluid and BALF contain distinct oxylipin profiles, which may have ramifications for the study of respiratory diseases. Specific protocols for sampling proximal and distal airways separately should be employed for lipid mediator studies.

Topics: Adolescent; Adult; Arachidonic Acid; Asthma; Biopsy; Bronchoalveolar Lavage Fluid; Bronchoscopy; Case-Control Studies; Exhalation; Female; Gene Expression Regulation; Healthy Volunteers; Humans; Hypersensitivity; Inflammation; Linoleic Acid; Lipids; Male; Nitric Oxide; Oxylipins; Young Adult

Topics: Arachidonic Acid; Breast Feeding; Child; Child, Preschool; Fatty Acids, Omega-6; Female; Humans; Hypersensitivity; Infant; Infant Nutritional Physiological Phenomena; Infant, Newborn; Linoleic Acid; Lung; Male; Pregnancy; Prenatal Exposure Delayed Effects; Respiratory Function Tests; T-Lymphocyte Subsets

It has been argued that a reduction in the Western diet of anti-inflammatory unsaturated lipids, such as n-3 polyunsaturated fatty acids, has contributed to the increase in the frequency and severity of allergic diseases.. We investigated whether feeding milk fat enriched in conjugated linoleic acid and vaccenic acids (VAs) ('enriched' milk fat), produced by supplementing the diet of pasture-fed cows with fish and sunflower oil, will prevent development of allergic airway responses.. C57BL/6 mice were fed a control diet containing soybean oil and diets supplemented with milk lipids. They were sensitized by intraperitoneal injection of ovalbumin (OVA) on days 14 and 28, and challenged intranasally with OVA on day 42. Bronchoalveolar lavage fluid, lung tissues and serum samples were collected 6 days after the intranasal challenge.. Feeding of enriched milk fat led to marked suppression of airway inflammation as evidenced by reductions in eosinophilia and lymphocytosis in the airways, compared with feeding of normal milk fat and control diet. Enriched milk fat significantly reduced circulating allergen-specific IgE and IgG1 levels, together with reductions in bronchoalveolar lavage fluid of IL-5 and CCL11. Treatment significantly inhibited changes in the airway including airway epithelial cell hypertrophy, goblet cell metaplasia and mucus hypersecretion. The two major components of enriched milk fat, cis-9, trans-11 conjugated linoleic acid and VA, inhibited airway inflammation when fed together to mice, whereas alone they were not effective.. Milk fat enriched in conjugated linoleic and VAs suppresses inflammation and changes to the airways in an animal model of allergic airway disease.

Topics: Allergens; Animals; Cell Survival; Chemokine CCL11; Eosinophils; Fats; Female; Hypersensitivity; Immunoglobulins; Interleukin-5; Linoleic Acid; Lung Diseases, Obstructive; Male; Mice; Mice, Inbred C57BL; Milk; Oleic Acids

The purpose of this study was to examine whether conjugated linoleic acid (CLA) supplementation in human diets would enhance indices of immune status as reported by others for animal models. Seventeen women, 20-41 yr, participated in a 93-d study conducted in two cohorts of 9 and 8 women at the Metabolic Research Unit of Western Human Nutrition Research Center. Seven subjects were fed the basal diet (19, 30, and 51% energy from protein, fat, and carbohydrate, respectively) throughout the study. The remaining 10 subjects were fed the basal diet for the first 30 d, followed by 3.9 g CLA (Tonalin)/d for the next 63 d. CLA made up 65% of the fatty acids in the Tonalin capsules, with the following isomeric composition: t10, c12, 22.6%; c11, t13, 23.6%; c9, t11, 17.6%; t8, c10, 16.6%; and other isomers 19.6%. Most indices of immune response were tested at weekly intervals, three times at the end of each period (stabilization/intervention); delayed-type hypersensitivity (DTH) to a panel of six recall antigens was tested on study day 30 and 90; all subjects were immunized on study day 65 with an influenza vaccine, and antibody titers were examined in the sera collected on day 65 and 92. None of the indices of immune status tested (number of circulating white blood cells, granulocytes, monocytes, lymphocytes, and their subsets, lymphocytes proliferation in response to phytohemagglutinin, and influenza vaccine, serum influenza antibody titers, and DTH response) were altered during the study in either dietary group. Thus, in contrast to the reports with animal models, CLA feeding to young healthy women did not alter any of the indices of immune status tested. These data suggest that short-term CLA supplementation in healthy volunteers is safe, but it does not have any added benefit to their immune status.

Topics: Adult; Antibodies; Body Weight; Cohort Studies; Diet; Dose-Response Relationship, Drug; Fatty Acids; Female; Humans; Hypersensitivity; Immune System; Influenza Vaccines; Leukocytes; Linoleic Acid; Lymphocytes; Placebos; Random Allocation; Time Factors

Topics: Dietary Fats; Humans; Hypersensitivity; Linoleic Acid; Prevalence

Respiratory histaminergic and cholinergic receptor function was investigated in isolated tracheal spirals of guinea pigs receiving different diets. Comparison was made between saline treated (controls) and Haemophilus influenzae treated animals in non sensitized conditions, the latter being a model for bronchial hyperreactivity, and in sensitized conditions, being a model for allergen induced bronchial hypersensitivity. The different semi-synthetic diets (35 energy% fat), varying in linoleic acid content (5.85, 11.25 and 22.05 en% fat) and one diet with low linoleic acid (3.55 en%) in which linolenic acid was added additionally (5.30 en%), exerted profound effects on tracheal reactivity to histamine. In sensitized animals the maximal induced histamine contraction was significantly diminished in the dietary group receiving 5.85 en% linoleic acid as compared with the other dietary groups (35% decrease in the H. influenzae-treated, 20-30% decrease in saline treated animals). Results in non-sensitized animals were similar, though less pronounced. No effect on food intake or growth of the animals could be demonstrated during the six week experimental periods. The carbachol induced contraction of the tracheal spirals of sensitized animals receiving low linoleic acid was also significantly decreased as compared to the other dietary groups (30% for saline treated and 20-30% for H. influenzae-treated animals). No difference in carbachol responsiveness could be detected between the different dietary groups under non-sensitized conditions. The results are discussed in view of the current concepts for bronchial hyperreactivity, especially in relation to eicosanoid involvement.

Topics: alpha-Linolenic Acid; Animals; Bronchial Diseases; Carbachol; Dietary Fats; Fatty Acids, Unsaturated; Guinea Pigs; Haemophilus influenzae; Histamine; Hypersensitivity; Linoleic Acid; Linoleic Acids; Linolenic Acids; Male; Muscle Contraction; Ovalbumin; Receptors, Cholinergic; Receptors, Histamine; Trachea

Topics: Arachidonic Acid; Humans; Hypersensitivity; Immune System Diseases; Linoleic Acid; Liver Diseases; Syndrome

Topics: Arachidonic Acid; Humans; Hypersensitivity; Immune System Diseases; Linoleic Acid; Liver Diseases; Syndrome