Effects of dietary n-3 or n-6 fatty acids on interleukin-1β-induced anxiety, stress, and inflammatory responses in rats

The present study demonstrated that an ω (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)-1β. Ethyl-EPA also reduced the rise in serum corticosterone induced by IL-1. The n-6 fatty acid ethyl-γ-linolenic acid (ethyl-GLA) had little effect on the IL-1-induced changes in behavior and the corticosterone concentration. Following IL-1β 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. The present study demonstrated that an ω (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)-1β. Ethyl-EPA also reduced the rise in serum corticosterone induced by IL-1. The n-6 fatty acid ethyl-γ-linolenic acid (ethyl-GLA) had little effect on the IL-1-induced changes in behavior and the corticosterone concentration. Following IL-1β 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. Long-chain polyunsaturated fatty acids synthesized from dietary precursors such as α-linolenic and linoleic fatty acids are important components of membrane phospholipids in microglia, neurons, and immune cells (1Horrobin D.F. Bennett C.N. Depression and bipolar disorder: relationships to impaired fatty acid and phospholipid metabolism and to diabetes, cardiovascular disease, immunological abnormalities, cancer, ageing and osteoporosis. Possible candidate genes.Prostaglandins Leukot. Essent. Fatty Acids. 1999; 60: 217-234Google Scholar, 2Horrobin D.F. Bennett C.N. New gene targets related to schizophrenia and other psychiatric disorders: enzymes, binding proteins and transport proteins involved in phospholipid and fatty acid metabolism.Prostaglandins Leukot. Essent. Fatty Acids. 1999; 60: 141-167Google Scholar). Free fatty acids released into the blood, or passing through the blood-brain barrier, can act at specific binding sites such as the peroxisome proliferator-activated receptor, ion channels, or at allosteric sites on various proteins (1Horrobin D.F. Bennett C.N. Depression and bipolar disorder: relationships to impaired fatty acid and phospholipid metabolism and to diabetes, cardiovascular disease, immunological abnormalities, cancer, ageing and osteoporosis. Possible candidate genes.Prostaglandins Leukot. Essent. Fatty Acids. 1999; 60: 217-234Google Scholar, 2Horrobin D.F. Bennett C.N. New gene targets related to schizophrenia and other psychiatric disorders: enzymes, binding proteins and transport proteins involved in phospholipid and fatty acid metabolism.Prostaglandins Leukot. Essent. Fatty Acids. 1999; 60: 141-167Google Scholar). Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), synthesized from α-linolenic acids (18:3, n-3), and γ-linolenic acid (GLA) and arachidonic acid (AA) from linoleic acids (20:4, n-6), play major roles in membrane fluidity, lipid peroxidation, eicosanoid production, receptor and channel functions, and gene expressions (1Horrobin D.F. Bennett C.N. Depression and bipolar disorder: relationships to impaired fatty acid and phospholipid metabolism and to diabetes, cardiovascular disease, immunological abnormalities, cancer, ageing and osteoporosis. Possible candidate genes.Prostaglandins Leukot. Essent. Fatty Acids. 1999; 60: 217-234Google Scholar, 2Horrobin D.F. Bennett C.N. New gene targets related to schizophrenia and other psychiatric disorders: enzymes, binding proteins and transport proteins involved in phospholipid and fatty acid metabolism.Prostaglandins Leukot. Essent. Fatty Acids. 1999; 60: 141-167Google Scholar, 3Peet M. Glen I. Horrobin D.F. Phospholipid Spectrum Disorder in Psychiatry. Marius Press, Lancashire, UK1999Google Scholar). Changes in the phospholipid content of neuronal membranes can result in changes in signal transduction, neurotransmitter release, enzyme activity, and in neurotransmitter receptor and ion channel functions (1Horrobin D.F. Bennett C.N. Depression and bipolar disorder: relationships to impaired fatty acid and phospholipid metabolism and to diabetes, cardiovascular disease, immunological abnormalities, cancer, ageing and osteoporosis. Possible candidate genes.Prostaglandins Leukot. Essent. Fatty Acids. 1999; 60: 217-234Google Scholar, 2Horrobin D.F. Bennett C.N. New gene targets related to schizophrenia and other psychiatric disorders: enzymes, binding proteins and transport proteins involved in phospholipid and fatty acid metabolism.Prostaglandins Leukot. Essent. Fatty Acids. 1999; 60: 141-167Google Scholar, 3Peet M. Glen I. Horrobin D.F. Phospholipid Spectrum Disorder in Psychiatry. Marius Press, Lancashire, UK1999Google Scholar). Such changes have been implicated in the etiology of mood disorder and stress response in humans and behavioral changes in animals (1Horrobin D.F. Bennett C.N. Depression and bipolar disorder: relationships to impaired fatty acid and phospholipid metabolism and to diabetes, cardiovascular disease, immunological abnormalities, cancer, ageing and osteoporosis. Possible candidate genes.Prostaglandins Leukot. Essent. Fatty Acids. 1999; 60: 217-234Google Scholar, 2Horrobin D.F. Bennett C.N. New gene targets related to schizophrenia and other psychiatric disorders: enzymes, binding proteins and transport proteins involved in phospholipid and fatty acid metabolism.Prostaglandins Leukot. Essent. Fatty Acids. 1999; 60: 141-167Google Scholar, 4Chalon S. Delion-Vancassel S. Belzung C. Guilloteau D. Leguisquet A.M. Besnard J.C. Durand G. Dietary fish oil affects monoaminergic neurotransmission and behavior in rats.J. Nutr. 1998; 128: 2512-2519Google Scholar, 5Maes M. Christophe A. Bosmans E. Lin A. Neels H. In humans, serum polyunsaturated fatty acid levels predict the response of proinflammatory cytokines to psychological stress.Biol. 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Dietary polyunsaturated fatty acids and inflammatory mediator production.Am. J. Clin. Nutr. 2000; 71: 343-348Google Scholar, 10Furse R.K. Rossetti R.G. Zurier R.B. Gammalinolenic acid, an unsaturated fatty acid with anti-inflammatory properties, blocks amplification of IL-1 beta production by human monocytes.J. Immunol. 2001; 167: 490-496Google Scholar). These diseases are associated with inflammation in the brain and disturbances in brain function (11Conquer J.A. Tierney M.C. Zecevic J. Bettger W.J. Fisher R.H. Fatty acid analysis of blood plasma of patients with Alzheimer's disease, other types of dementia, and cognitive impairment.Lipids. 2000; 35: 1305-1312Google Scholar, 12Monsonego A. Maron R. Zota V. Selkoe D.J. Weiner H.L. Immune hyporesponsiveness to amyloid beta-peptide in amyloid precursor protein transgenic mice: implications for the pathogenesis and of Alzheimer's 2001; Scholar, H.L. S. A. in multiple sclerosis to on Am. J. 1999; Scholar). 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Nutr. 2000; 71: 343-348Google Scholar, effects of dietary lipids on immune 2000; Scholar). By contrast, which the precursor of been to inflammation of eicosapentaenoic acid to γ-linolenic serum acid in Nutr. 2000; Scholar). The n-3 fatty acids such as a precursor of the of antibodies and proinflammatory cytokines, and inflammatory by membrane AA and eicosanoid M.J. Gibson R.A. Cleland L.G. Dietary polyunsaturated fatty acids and inflammatory mediator production.Am. J. Clin. Nutr. 2000; 71: 343-348Google Scholar, fatty and 2001; Scholar). diet with n-6 fatty acids been to increase behavior in with n-3 fatty acids reduced the stress response and and M. E. of polyunsaturated fatty acids in behavior, in the and brain protein Nutr. 1998; 128: Scholar, A. M. H. of n-3 fatty acid alterations of behavior in the of n-6 fatty acids as Lipid Res. 2001; Scholar). n-3 and n-6 fatty acids also with that ethyl-EPA of an effect which related to an increase in AA D.F. Bennett C.N. acid and arachidonic and not the to Leukot. Essent. Fatty Acids. whereas a combination of and greater antiinflammatory effects or alone of eicosapentaenoic acid to γ-linolenic serum acid in Nutr. 2000; Scholar). the n-3 and n-6 fatty acids at would appear to important for membrane and functions and for signal (1Horrobin D.F. Bennett C.N. Depression and bipolar disorder: relationships to impaired fatty acid and phospholipid metabolism and to diabetes, cardiovascular disease, immunological abnormalities, cancer, ageing and osteoporosis. Possible candidate genes.Prostaglandins Leukot. Essent. Fatty Acids. 1999; 60: 217-234Google Scholar, 2Horrobin D.F. Bennett C.N. New gene targets related to schizophrenia and other psychiatric disorders: enzymes, binding proteins and transport proteins involved in phospholipid and fatty acid metabolism.Prostaglandins Leukot. Essent. Fatty Acids. 1999; 60: 141-167Google Scholar, 3Peet M. Glen I. Horrobin D.F. Phospholipid Spectrum Disorder in Psychiatry. Marius Press, Lancashire, UK1999Google Scholar). to the the n-3 and n-6 fatty The inflammatory response or attenuated by the polyunsaturated fatty acids linked to the of the or anti-inflammatory the proinflammatory been to stress and anxiety-like behavior in C. H. of the effects of and administration on endocrine and immune in the 1998; Scholar, C. H. of and following or 1999; Scholar, C. The effect of and IL-1 on implications for the and Scholar). cytokine the to the secretion of from the IL-1β also the of and The changes are similar to those to a C. H. of and following or 1999; Scholar, S. H. of on plasma and in 1998; Scholar). have demonstrated that and IL-1β can the of protein and to proinflammatory cytokines and antibodies that result in brain inflammation J.T. S. H. of the amyloid precursor protein by through 1999; Scholar, S. inflammation in the brain and Neurol. 1999; Scholar). of the effects of IL-1β on brain function are by by of the and also following immune D. M. S. A. A. as inflammatory the blood-brain Scholar). of been to the IL-1-induced of corticosterone and also the behavioral response to A. C. for an in the of by Scholar). The that a related to such as stress and n-3 and n-6 fatty acids can function and inflammatory response, can n-3 or n-6 fatty acids or a combination of changes induced by brain and are the the types of fatty acids the inflammatory In the present the effect of with fatty acids and ethyl-GLA, combination of and or and on and inflammatory response induced in rats by the administration of IL-1β was rats from and in a at for the rats into of rats and with of for oil was to rats as a The oil with of of fatty acid ethyl-GLA, or and oil with a combination of and or a combination of and The rats in with or IL-1β by the intracerebroventricular The for the the in which animals the Following the of the for the intracerebroventricular administration, and following or IL-1 administration for The basal from oil and ethyl-EPA, ethyl-GLA, and AA oil at The basal not fatty of the fatty acid was to of the basal The of in oil was to a and in a The basal diet was with the oil by the of the of the other fatty The was of and at in basal in a rats with and was for of the was at a and of the a The was to and to the with was into the C. and immunological to administration. a mediator of Scholar). The animals to for IL-1β was from and in at of and for intracerebroventricular administration. and with a for the of the intracerebroventricular the IL-1β or in a was into an that was to a the of a the was into the and IL-1 or was into the brain a of The was to the for and was to the on the with or IL-1β behavioral C. H. of the effects of and administration on endocrine and immune in the 1998; Scholar). The was of and of a with a of of was on the of the for was the of the in the of the The and and the of into the of the for a of by of a J.A. in behavior in the and Scholar). The was with had been The elevated plus of an elevated from the and of and The and The was on the by the at the of The was by a in the of the the of was on the of the maze, the S. M. of in an elevated as a of anxiety in the Scholar). The into and and the on a The with by with or without The blood with and a the blood was with into with and for in a at the at for The was and at the cytokine C. Lin A. S. C. R. G. Bosmans E. S. A. de R. M. The inflammatory response and the of plasma in patients with and major 1998; Scholar). The of IL-10 and was by a and enzyme as C. Lin A. S. C. R. G. Bosmans E. S. A. de R. M. The inflammatory response and the of plasma in patients with and major 1998; Scholar). from blood for the corticosterone with a corticosterone for and of and and on an and the of the and sites by the brain from animals in which the to the by by for the and The was from was at a of are as of n-3 and n-6 fatty acids on behavior in “open field” following intracerebroventricular administration of oil the with the oil IL-1 oil IL-1 oil IL-1 arachidonic eicosapentaenoic γ-linolenic the with the oil IL-1 in a arachidonic eicosapentaenoic γ-linolenic no the in the of with for the of of oil and of of oil and of oil and AA of ethyl-EPA, and of of ethyl-EPA, and AA following the of the the of in the with oil was significantly with the was significantly attenuated in the with the combination of ethyl-EPA and The of was significantly reduced in rats intracerebroventricular IL-1β administration for or on not with ethyl-EPA and in combination with ethyl-GLA, the induced by IL-1β administration was Ethyl-EPA in combination with AA or fatty acid no effect on the of or IL-1 administration with for not behavioral changes in the “open field” intracerebroventricular administration. In the intracerebroventricular IL-1β administration significantly reduced the of of and analysis that IL-1-induced changes attenuated by the n-3 and n-6 fatty acids The to levels in animals with ethyl-EPA with the in rats with oil diet and with IL-1β Ethyl-GLA alone attenuated the in and the in in the rats with IL-1β The combination of ethyl-EPA with or or AA alone not significantly the effects of IL-1β In the elevated plus maze, rats with AA oil and with showed a in the of the of into with the in animals with oil with oil and with intracerebroventricular IL-1β significantly the of in with rats with oil alone These anxiety-like changes in the elevated plus attenuated by ethyl-EPA The other fatty alone or in not IL-1-induced changes of the not significantly the serum concentrations of corticosterone following but increase in corticosterone was in rats with AA oil increase in corticosterone concentrations in the supplemented diet with ethyl-GLA, or the combination of ethyl-EPA and ethyl-EPA alone significantly the of corticosterone induced by IL-1β administration from the blood of animals with oil intracerebroventricular not changes in the of or IL-10 in animals with or a combination of and The diet from and blood, AA enhanced in blood In blood, IL-1β administration significantly increased in animals with oil with the on the oil diet was by a diet with ethyl-EPA, or a combination of ethyl-EPA and ethyl-GLA, but not by other fatty acids In blood, IL-1β administration also induced a increase in in animals with oil or AA oil was by ethyl-EPA, ethyl-GLA, or a combination of ethyl-EPA and IL-10 from or blood not the following In blood, intracerebroventricular IL-1β administration induced a in IL-10 in with the of rats with a combination of ethyl-EPA and ethyl-GLA, in which IL-10 was significantly that in animals oil alone In blood, IL-1β significantly IL-10 in the oil whereas in animals with ethyl-EPA or ethyl-GLA, the of IL-10 by IL-1 was significantly In the present the administration of IL-1β significantly induced types of The an response and the a The response reduced enhanced and of antiinflammatory cytokine The response of a in the of the of into and in the of the elevated plus maze, and a in and in the “open The increase in serum corticosterone concentrations following IL-1β administration also a of a stress supplemented with n-3 or n-6 fatty or a combination of effects on behavior and inflammatory response, which related to roles that fatty acids play in the of inflammatory response and The anti-inflammatory effects of n-3 fatty acid have been Dietary supplementation with the production of proinflammatory cytokines and and other immune functions in human and animals effects of dietary lipids on immune 2000; Scholar, of inflammation and cytokine production by dietary fatty Nutr. Scholar, E. Cleland L.G. Gibson R.A. M. M.J. effects of a diet with n-3 fatty J. Clin. Nutr. 2000; Scholar). fish diet been to and the production of and proinflammatory cytokines induced in rats by the of D. M.J. Dietary n-3 fatty acids behavior in and J. Scholar). have that the effect of IL-1 attenuated by n-3 fatty acids effects of dietary lipid on immune 2000; Scholar). In the present the of was attenuated in the the ethyl-EPA diet and significantly in the with the combination of ethyl-EPA and The in the growth was in animals with ethyl-EPA or the combination of ethyl-EPA and The effect of the combination was These that a combination of ethyl-EPA and greater antiinflammatory effects ethyl-EPA alone for from and that a diet reduced the production of lipid mediators of inflammation and attenuated of inflammatory diseases of eicosapentaenoic acid to γ-linolenic serum acid in Nutr. 2000; Scholar, Zurier R.B. of rheumatoid with J. Scholar). been also to IL-1β from R.K. Rossetti R.G. Zurier R.B. administration of acid, an unsaturated fatty acid with anti-inflammatory properties, production by human monocytes.J. Clin. Immunol. Scholar). that AA of eicosapentaenoic acid to γ-linolenic serum acid in Nutr. 2000; and that the of AA to an increase in proinflammatory cytokines the M.J. Gibson R.A. Cleland L.G. Dietary polyunsaturated fatty acids and inflammatory mediator production.Am. J. Clin. Nutr. 2000; 71: 343-348Google Scholar, effects of dietary lipids on immune 2000; Scholar). a combination of and been to the of AA and the inflammatory mediator in the serum blocks activity, the in AA of eicosapentaenoic acid to γ-linolenic serum acid in Nutr. 2000; Scholar). In the present the ethyl-EPA and combination showed a greater effect ethyl-EPA or alone in the of following or IL-1β administration. the combination of ethyl-EPA and AA diet significantly in caused by IL-1. The effects of fatty acids on or related to the effects of fatty acids on inflammatory been in the present study that intracerebroventricular IL-1β administration induced a increase in the of and a in IL-10 in blood in rats the rats with a diet with ethyl-EPA or combination of and changes with or a combination with ethyl-EPA, not significantly inflammatory changes and also not the IL-1-induced in the the which reduced and increased IL-10 in blood significantly the induced by was also that the antiinflammatory effect of ethyl-EPA was greater the combination of and Thus, a the effects of fatty acids on the inflammatory response and the in the by IL-1. The “open field” to response to a and J.A. in behavior in the and Scholar). In the “open IL-1β administration significantly reduced and in the animals with the diet of In the elevated plus maze, a of the of into and on was following IL-1β administration in animals with the In addition, the stress corticosterone was significantly increased following the cytokine These that IL-1 induced a stress and anxiety-like and have similar C. H. of the effects of and administration on endocrine and immune in the 1998; Scholar, C. The effect of and IL-1 on implications for the and Scholar, S. H. of on plasma and in 1998; Scholar). The present study that an diet significantly attenuated the proinflammatory stress and anxiety-like The from the present study that the behavioral of ethyl-EPA on stress and anxiety-like behavior related to the in the stress Thus, ethyl-EPA significantly the of corticosterone levels induced by IL-1β and also the behavior in “open field” and elevated plus maze. Ethyl-GLA or in combination with ethyl-EPA, not the increase in corticosterone levels or the the diet increased corticosterone and induced anxiety-like behavior the of into in the elevated plus by the that an increase in the of by IL-1 on the of of n-6 C. effect of on secretion in the by Scholar). by have that diet increased behavior in rats and that a diet with AA oil increased corticosterone concentrations M. E. of polyunsaturated fatty acids in behavior, in the and brain protein Nutr. 1998; 128: Scholar, of arachidonic acid in the of the inflammatory response in J. Nutr. 1998; Scholar). The n-6 fatty acid not the stress response and corticosterone n-3 fatty acids have been to cardiovascular and following to stress of arachidonic acid in the of the inflammatory response in the J. Nutr. 1998; Scholar, G. of arachidonic acid and the effects of on in Scholar, M. Effects of dietary acid on blood and in 1998; Scholar, D. D. D. H. R. A. a dietary fatty acid to the effect of the psychological 1998; Scholar). In or in to psychological was and was which that increased AA play a in stress or M. Christophe A. Bosmans E. Lin A. Neels H. In humans, serum polyunsaturated fatty acid levels predict the response of proinflammatory cytokines to psychological stress.Biol. Psychiatry. 2000; 47: 910-920Google Scholar, R. M. J. Horrobin D. polyunsaturated fatty acid levels in the diet and in blood membranes of 1998; Scholar, M. R. Christophe A. R. H. Fatty acid in major in and increased in and Scholar). The from the present study showed that AA increased corticosterone and PGE2, and of into the which was of the The effect of ethyl-EPA on corticosterone from anti-inflammatory effects on the fatty ethyl-EPA the antiinflammatory in effects on and which significantly with of corticosterone and of stress and anxiety-like Ethyl-GLA or in combination with a antiinflammatory not the corticosterone induced by and only reduced anxiety-like AA increased and corticosterone and increased anxiety-like IL-1β changes in the inflammatory response and corticosterone secretion through the of and receptor A. C. for an in the of by Scholar, S. R. of human prostaglandin E a a 1999; Scholar, M. C. A. of the prostaglandin receptor in the to sites of Neurol. 2000; Scholar). cytokine also gene of the receptor in the brain J. S. and of the the and in the brain and neuronal to J. 1999; Scholar). The by which ethyl-EPA the of eicosanoid M.J. Gibson R.A. Cleland L.G. Dietary polyunsaturated fatty acids and inflammatory mediator production.Am. J. Clin. Nutr. 2000; 71: 343-348Google Scholar, effects of dietary lipids on immune 2000; Scholar, of inflammation and cytokine production by dietary fatty Nutr. whereas the in corticosterone secretion following stress by the combination of and from a in the of the precursor of corticosterone S. S. Fatty acid stress changes in and J. 2000; Scholar). The of effect of alone or in combination with ethyl-EPA on the behavior by the induced of AA that in in corticosterone and M.J. Gibson R.A. Cleland L.G. Dietary polyunsaturated fatty acids and inflammatory mediator production.Am. J. Clin. Nutr. 2000; 71: 343-348Google Scholar, of arachidonic acid in the of the inflammatory response in J. Nutr. 1998; Scholar). In a that but significantly and changes induced by IL-1β C. fatty acids IL-1 caused and stress response in Scholar). the of that inflammatory in the In addition, to no on n-3 and n-6 by other that of n-3 to n-6 S. of and in the by of α-linolenic and linoleic of the Scholar). The that a in the present study on the following in a the not IL-1 induced have that oil in which the of n-3 to n-6 IL-1-induced changes C. fatty acids IL-1 caused and stress response in Scholar, M. and effects of and Am. Coll. Nutr. Scholar). have that n-6 in the brain a n-3 and n-6 or was to behavioral induced by n-3 deficiency A. M. H. of n-3 fatty acid alterations of behavior in the of n-6 fatty acids as Lipid Res. 2001; Scholar). IL-1β inflammation increase n-6 and in the present a of of not significantly of behavioral and inflammatory In a of ethyl-GLA, and and or In the present study demonstrated that n-3 fatty acid ethyl-EPA at of dietary significantly stress and anxiety-like behavior, stress and inflammatory in and diet at the significantly increased and IL-10 induced by IL-1β in blood but not significantly the elevated corticosterone and stress and anxiety-like AA supplemented diet significantly increased and corticosterone and induced anxiety-like behavior in the elevated plus maze. n-6 fatty acid an effect on IL-1-induced The combination of ethyl-EPA and the of or IL-1β administration and inflammatory changes, but not significantly the corticosterone and behavior induced by The combination of ethyl-EPA and AA not of the changes induced by These that fatty acids at alone in the of stress and anxiety-like behavior, which increased by The of antiinflammatory effects of fatty acids on IL-1-induced changes in the of and IL-10 as ethyl-EPA ethyl-EPA the combination of and was for following a and IL-1 administration. The A. G. for the to study to are also to for with and was by and arachidonic acid eicosapentaenoic acid γ-linolenic acid interleukin prostaglandin E2

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