Biomaterial Database

Manipulation of the acute inflammatory response by dietary polyunsaturated fatty acid modulation. 1990

J B Lefkowith, and A Morrison, and V Lee, and M Rogers

Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.

Dietary polyunsaturated fatty acid modulation has been used as an anti-inflammatory strategy in experimental models of disease as well as in clinical trials. To elucidate the mechanisms underlying the anti-inflammatory effects of manipulating dietary polyunsaturated fatty acids, the in vivo effects of essential fatty acid (EFA) deficiency and (n-3) fatty acid supplementation were contrasted using a model of acute inflammation induced by the i.p. injection of zymosan into mice. Both diets led to a substantial decrease in tissue (n-6) fatty acid content. EFA deficiency was also characterized by the accumulation of (n-9) fatty acids, particularly 20:3 (n-9), the fatty acid that uniquely characterizes the deficiency state. Dietary (n-3) fatty acid supplementation led instead to marked increases in (n-3) fatty acids, especially 20:5 (n-3). With respect to the antiinflammatory effects of the two diets, EFA deficiency, but not (n-3) fatty acid supplementation, depleted levels of resident peritoneal macrophages. EFA deficiency was also more effective than (n-3) fatty acid supplementation in inhibiting the influx of polymorphonuclear neutrophils in response to zymosan. The effect of the two diets on the in vivo generation of leukotriene(LT)B also differed markedly. EFA deficiency completely inhibited the synthesis of LTB. Dietary (n-3) fatty acid supplementation, in contrast, reduced the production of LTB4 by only 50%. With (n-3) fatty acid supplementation LTB5 was produced. The more modest effect of (n-3) fatty acid supplementation in decreasing LTB4 generation was not due to blockade of the cyclooxygenase pathway. EFA deficiency, but not (n-3) fatty acid supplementation, was associated with the decreased synthesis of thromboxane. Although dietary fatty acid modulation has been shown to diminish platelet activating factor (PAF) synthesis, studies using the PAF receptor blocker, L659989, established that PAF was not a significant factor in the elicitation of leukocytes in this model of inflammation. In summary, the anti-inflammatory effect of EFA deficiency was more marked that that of dietary (n-3) fatty acid supplementation in acute inflammation. This difference in anti-inflammatory potential appeared to be due to either the greater effect of EFA deficiency in decreasing levels of resident peritoneal macrophages or in suppressing the in vivo generation of LTB4.

UI	MeSH Term	Description	Entries
D007249	Inflammation	A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.	Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D007975	Leukotriene B4	The major metabolite in neutrophil polymorphonuclear leukocytes. It stimulates polymorphonuclear cell function (degranulation, formation of oxygen-centered free radicals, arachidonic acid release, and metabolism). (From Dictionary of Prostaglandins and Related Compounds, 1990)	5,12-HETE,5,12-diHETE,LTB4,Leukotriene B,Leukotriene B-4,Leukotrienes B,5,12 HETE,5,12 diHETE,B-4, Leukotriene,Leukotriene B 4
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008264	Macrophages	The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)	Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D008810	Mice, Inbred C57BL	One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.	Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D010980	Platelet Membrane Glycoproteins	Surface glycoproteins on platelets which have a key role in hemostasis and thrombosis such as platelet adhesion and aggregation. Many of these are receptors.	PM-GP,Platelet Glycoprotein,Platelet Membrane Glycoprotein,PM-GPs,Platelet Glycoproteins,Glycoprotein, Platelet,Glycoprotein, Platelet Membrane,Glycoproteins, Platelet,Glycoproteins, Platelet Membrane,Membrane Glycoprotein, Platelet,Membrane Glycoproteins, Platelet,PM GP
D011956	Receptors, Cell Surface	Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.	Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D004041	Dietary Fats	Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados.	Fats, Dietary,Dietary Fat,Fat, Dietary
D005228	Fatty Acids, Essential	Long chain organic acid molecules that must be obtained from the diet. Examples are LINOLEIC ACIDS and LINOLENIC ACIDS.	Acids, Essential Fatty,Essential Fatty Acids
D005231	Fatty Acids, Unsaturated	FATTY ACIDS in which the carbon chain contains one or more double or triple carbon-carbon bonds.	Fatty Acids, Polyunsaturated,Polyunsaturated Fatty Acid,Unsaturated Fatty Acid,Polyunsaturated Fatty Acids,Acid, Polyunsaturated Fatty,Acid, Unsaturated Fatty,Acids, Polyunsaturated Fatty,Acids, Unsaturated Fatty,Fatty Acid, Polyunsaturated,Fatty Acid, Unsaturated,Unsaturated Fatty Acids