Increased PUFA Content and 5-Lipoxygenase Pathway Expression Are Associated with Subcutaneous Adipose Tissue Inflammation in Obese Women with Type 2 Diabetes.

Obese women with type 2 diabetes mellitus (T2DM) have more inflammation in their subcutaneous white adipose tissue (sWAT) than age-and-BMI similar obese women with normal glucose tolerance (NGT). We aimed to investigate whether WAT fatty acids and/or oxylipins are associated with the enhanced inflammatory state in WAT of the T2DM women. Fatty acid profiles were measured in both subcutaneous and visceral adipose tissue (vWAT) of 19 obese women with NGT and 16 age-and-BMI similar women with T2DM. Oxylipin levels were measured in sWAT of all women. Arachidonic acid (AA) and docosahexaenoic acid (DHA) percentages were higher in sWAT, but not vWAT of the T2DM women, and AA correlated positively to the gene expression of macrophage marker CD68. We found tendencies for higher oxylipin concentrations of the 5-LOX leukotrienes in sWAT of T2DM women. Gene expression of the 5-LOX leukotriene biosynthesis pathway was significantly higher in sWAT of T2DM women. In conclusion, AA and DHA content were higher in sWAT of T2DM women and AA correlated to the increased inflammatory state in sWAT. Increased AA content was accompanied by an upregulation of the 5-LOX pathway and seems to have led to an increase in the conversion of AA into proinflammatory leukotrienes in sWAT.

Bradykinin and cysteinyl leukotriene concentrations in cell-salvaged blood before and after passage through negatively charged filters during clinical use in cancer patients: a pilot study.

It has been suggested that giving cell-salvaged blood through a leucocyte depletion filter can cause hypotension due to bradykinin released when factor XII and platelets are activated by the negatively charged surface of the filter. We measured the concentration of bradykinin and cysteinyl leukotrienes in cell-salvaged blood sampled before and after passage through a negatively charged leucodepletion filter in 24 consecutive patients with gynaecological or bowel cancer undergoing elective surgery with cell salvage. In no case was an increase in bradykinin concentration observed after passage through the filter; in 23 patients the post-filtration bradykinin concentration was zero (p = 0.007). The change in the concentration of cysteinyl leukotrienes detected during passage across the filter was not statistically significant (p = 0.1). Our findings do not support the suggestion that either bradykinin or cysteinyl leukotrienes are generated in cell-salvaged blood during passage through leucodepletion filters.

[Relationship between cysteinyl leukotriene in exhaled breath condensate and the severity of asthma in adult asthmatics in Japan].

BACKGROUND: The measurement of several mediators in exhaled breath condensate (EBC) can be useful as the biomarker for asthma. But there are a few reports about EBC of asthmatics in Japan. AIM: We examined the safety of the collection of EBC and the utility of cysteinyl leukotriene (cysLTs) in EBC as the biomarker of asthma. METHODS: Fifty-three asthmatics and eleven subjects without asthma were recruited. After the measuring of exhaled nitric oxide (eNO) and spirometory, EBC were collected. The levels of cysLTs in EBC were measurement by ELISA within 2 months. RESULTS: The collection of EBC did not induce any other symptoms in all subjects. In 48 subjects, the collection significantly increased their FEV1 and MMF level (DeltaFEV1: 2.27+/-0.77%, DeltaMMF 14.6+/-3.92% (mean+/-SEM). The level of cysLTs in EBC on asthmatics treated with high-dose ICS was significantly high compared with control group (p=0.0034), steroid-naïve asthmatics or asthmatics treated with low-dose ICS (steroid naive vs. high dose ICS, p=0.041, low dose ICS vs. high dose ICS, p=0.021). The relationship between cysLTs in EBC and the levels of LTE4 in urine was significantly correlated (n=34, r=0.32, p=0.0435). The relationship between cysLTs in EBC and the levels of eNO was significantly correlated only in steroid-naïve asthmatics (r=-0.57, p=0.0369). There was no relationship between cysLTs in EBC and FEV1, or log PC20Ach. CONCLUSION: The collection of EBC was perfectly non-invasive. The level of cysLTs can be useful as a biomarker of asthma.

Effect of a Chinese herbal formula, Shi-Bi-Lin, on an experimental model of allergic rhinitis.

BACKGROUND: Jia Wei Cang Er Zi San, a traditional Chinese herbal formula, has been used to treat allergic rhinitis (AR) for several centuries. However, its effect on experimental animal models and its therapeutic mechanism remain unclear. OBJECTIVE: To study the effect of Shu-Bi-Lin, a modified Jia Wei Cang Er Zi San, on an animal model of AR. METHODS: Shu-Bi-Lin was administered to the guinea pig model of AR. Meanwhile, an antihistamine-treated group for the treatment control, an ovalbumin-sensitized and untreated group for the positive control, and a sham-sensitized, sham-challenged group for the sham control were studied in parallel. Symptomatic and some pathophysiologic variables were evaluated. RESULTS: Sneezing and nasal scratching after challenges were significantly ameliorated in the Shu-Bi-Lin-treated group compared with the ovalbumin-sensitized and untreated group, but rhinorrhea volume was not reduced. Shu-Bi-Lin significantly suppressed the production of IgG1 in the passive cutaneous anaphylaxis test. The thromboxane B2 level in nasal lavage fluid was significantly deceased in the Shu-Bi-Lin-treated group; however, the reduction in histamine and peptide leukotriene levels did not reach statistical significance. In addition, eosinophil infiltration and endothelial nitric oxide synthase immunoreactivity in the nasal tissues were reduced in the Shu-Bi-Lin-treated group. CONCLUSIONS: Shu-Bi-Lin could alleviate the nasal symptoms of AR, and its mechanism might be related to its inhibitory effect on type I anaphylaxis reactions and eosinophil infiltration in the nasal tissues, as well as the inhibition of some mediators related to AR.

Anti-allergic properties of Cissampelos sympodialis and its isolated alkaloid warifteine.

Development of new agents capable of regulating eosinophilic inflammation can uncover novel therapeutic approaches for the treatment of allergic diseases, such as asthma. Here, we evaluated the anti-allergic properties of an extract of the Brazilian Menispermaceae Cissampelos sympodialis, focusing on its effects on allergic eosinophilia. By studying two models of allergic inflammation, an asthma model and the allergic pleurisy in actively sensitized Balb/c mice, we observed that the oral pre-treatment with C. sympodialis reduced pleural eosinophil influx triggered by allergen challenge in a dose-dependent manner. The mechanism involved in C. sympodialis inhibitory effect appeared to be independent of a direct effect on eosinophil locomotory machinery, but depend on a blockage of eotaxin production, a key eosinophil chemoattractant with important roles in allergic reactions. C. sympodialis was also able to affect eosinophil activation, as attested by its ability of inhibiting formation of new cytoplasmic lipid bodies and the secretion of cysteinyl leukotrienes. The alkaloid warifteine isolated from the C. sympodialis extract represents an active component responsible for the anti-eosinophilic effects of the extract, since warifteine was able to reproduce C. sympodialis inhibitory effects on allergic eosinophilia and cysteinyl leukotrienes production. Of interest, C. sympodialis and warifteine post-treatments also effectively inhibited eosinophilic reaction observed after allergic challenge. Therefore, C. sympodialis/warifteine may be a promising anti-allergic therapy, inasmuch as it presents potent anti-eosinophil and anti-leukotrienes activities.

Free arachidonic versus eicosapentaenoic acid differentially influences the potency of bacterial exotoxins to provoke myocardial depression in isolated rat hearts.

OBJECTIVE: Staphylococcal alpha-toxin and Escherichia coli hemolysin (ECH) evoke cardiac dysfunction in isolated rat hearts by provoking myocardial synthesis of arachidonic acid-derived thromboxane A2 or the cysteinyl-leukotrienes, LTC4, LTD4, and LTE4, respectively. We investigated whether low doses of either toxin, which fail to induce cardiac depression by themselves, induce cardiac dysfunction when combined with free arachidonic acid. DESIGN: Prospective, experimental study. SETTING: Research laboratory at a university hospital. SUBJECTS: Isolated hearts from male Wistar rats. INTERVENTIONS: Hearts were perfused with low doses of ECH or alpha-toxin in the absence or presence of arachidonic acid or the alternative eicosanoid precursor eicosapentaenoic acid (EPA). MEASUREMENTS AND MAIN RESULTS: Application of low-dose ECH with arachidonic acid increased coronary perfusion pressure, depressed left ventricular contractile function, provoked electrical instability, and induced a release of creatine kinase concomitant with the liberation of LTC4, LTD4, and LTE4 into the perfusate. All events were abolished when formation of cysteinyl-leukotrienes was blocked by the 5-lipoxygenase activity inhibitor MK-886, targeting 5-lipoxygenase activating protein. In the presence of arachidonic acid, low doses of alpha-toxin caused an increase in cerebral perfusion pressure and a decline of contractile performance, attributable to the release of thromboxane A2, as both events were mitigated by the cyclooxygenase-inhibitor indomethacin. High doses of ECH caused cardiac dysfunction even in the absence of arachidonic acid. However, in the presence of EPA, the cardiodepressant effect of ECH was blunted. Release of EPA-derived LTE5 at the expense of arachidonic acid-derived LTC4, LTD4, and LTE4 was noted in these hearts. CONCLUSIONS: The potency of the bacterial exotoxins ECH and alpha-toxin to cause coronary vasoconstriction and myocardial depression is dependent on the availability of free arachidonic acid and may be influenced by supplying omega-3 fatty acids as alternative lipid precursors.

Improved fatty acid and leukotriene pattern with a novel lipid emulsion in surgical patients.

OBJECTIVE: We assessed the effects of a novel lipid emulsion with reduced content of n-6 fatty acids (FA), increased share of MUFA and n-3 FA and supplemental vitamin E on fatty acid and leukotriene pattern in surgical patients. METHODS: In a double-blind, randomized study 33 patients received isonitrogenous, isocaloric TPN over 5 postoperative days following major abdominal surgery. 19 patients received the new SMOFlipid 20% and 14 patients a standard soybean oil emulsion (Lipovenoes 20%, both Fresenius Kabi), each 1.5 g fat/kg body weight (BW)/d. Routine lipid biochemistry, plasma tocopherol, fatty acid pattern in plasma phospholipids, as well as leukotriene (LT) release in leukocytes were assessed. Additionally, fatty acid pattern in leukocyte and platelet phospholipids were analysed, but results are not presented. RESULTS: On day 6, plasma alpha-tocopherol (34.2 +/- 10.3 vs. 17.6 +/- 2.9 micromol/L) and, in plasma PL, total n-3 FA were higher (11.1 +/- 1.9 vs. 4.9 +/- 0.9 mol%; p < 0.05) and total n-6 FA lower (23.8 +/- 2.2 vs. 31.8 +/- 1.7 mol%; P < 0.05); the ratio n-3/n-6 FA being elevated (0.5 +/- 0.1 vs. 0.2 +/- 0.0 p < 0.05) with SMOFlipid compared to the soybean oil emulsion. The shares of EPA (3.3+/-1.0 vs. 0.4+/-0.2 mol%; p<0.05) and DHA (6.9 +/- 1.8 vs. 3.7 +/- 0.8 mol%; p < 0.05) were highly increased but that of arachidonic acid (AA) was unchanged with SMOFlipid while the ratio EPA/AA was increased (0.7 +/- 0.2 vs. 0.1 +/- 0.0 p < 0.05). LTB(5) release was enhanced on day 6 (8.1 +/- 5.3 vs. 1.8 +/- 3.8 pmol/10(7) PMN, p < 0.05) and liberation of LTB(4) was lowered, yet not significantly with SMOFlipid (124.0 +/- 51.2 vs. 152.1 +/- 68.8 pmol/10(7) PMN). Length of hospital stay was significantly shorter with SMOFlipid (13.4 +/- 2.0 vs. 20.4 +/- 10.0 days, p < 0.05). CONCLUSION: Treatment with the new emulsion SMOFlipid is well tolerated and modulates FA and leukotriene pattern suggesting favourable anti-inflammatory effects and further clinical benefits.

Leukotriene and prostanoid pathway enzymes in bronchial biopsies of seasonal allergic asthmatics.

Cysteinyl-leukotrienes and prostaglandin D2 generated by the 5-lipoxygenase (5-LO) and cyclooxygenase (COX) pathways, respectively, cause bronchoconstriction, leukocyte recruitment, and bronchial hyperresponsiveness in asthma. We characterized the cellular expression of 5-LO and COX enzymes using immunohistochemistry on bronchial biopsies from 12 allergic asthmatic patients before and during seasonal exposure to birch pollen. Bronchial responsiveness (p = 0.004) and symptoms (p < 0.005) increased and peak expiratory flow (PEF; p < or = 0.02) decreased in the pollen season. In-season biopsies had 2-fold more cells immunostaining for 5-LO (p = 0.02), 5-LO-activating protein (FLAP; p = 0.04), and leukotriene (LT)A4 hydrolase (p = 0.05), and 4-fold more for the terminal enzyme for cysteinyl-leukotriene synthesis, LTC4 synthase (p = 0.02). Immunostaining for COX-1, COX-2, and PGD2 synthase was unchanged. Increased staining for LTC4 synthase was due to increased eosinophils (p = 0.035) and an increased proportion of eosinophils expressing the enzyme (p = 0.047). Macrophages also increased (p = 0.019), but mast cells and T-lymphocyte subsets were unchanged. Inverse correlations between PEF and 5-LO(+) cell counts link increased expression of 5-LO pathway enzymes in eosinophils and macrophages within the bronchial mucosa to deterioration of lung function during seasonal allergen exposure.

Workup-dependent formation of 5-lipoxygenase inhibitory boswellic acid analogues.

Pentacyclic triterpenes from the 11-keto-boswellic acid series were identified as the active principal ingredients of Boswellia resin, inhibiting the key enzyme of leukotriene biosynthesis, 5-lipoxygenase (5-LO). Of the genuine boswellic acids hitherto characterized, 3-O-acetyl-11-keto-beta-boswellic acid, AKBA (1), proved to be the most potent inhibitor of 5-LO. In the course of purification of further boswellic acid derivatives from Boswellia resin, we observed the degradation of the natural compound 3-O-acetyl-11-hydroxy-beta-boswellic acid (2) to the thermodynamically more stable product 3-O-acetyl-9, 11-dehydro-beta-boswellic acid (4). The metastable intermediate of this conversion, under moderate conditions of workup in methanolic solutions, was identified as 3-O-acetyl-11-methoxy-beta-boswellic acid (3). The novel artifactual boswellic acid derivatives inhibited 5-LO product formation in intact cells with different characteristics: 4 almost totally abolished 5-LO activity, with an IC(50) of 0.75 microM, whereas 3 and 9,11-dehydro-beta-boswellic acid (5), the deacetylated analogue of 4, were incomplete inhibitors. The data suggest that the conditions chosen for the workup of Boswellia extracts could significantly influence the potency of their biological actions and their potential therapeutic effectiveness.

Is administration of n-3 fatty acids by mucosal enema protective against trinitrobenzene-induced colitis in rats?

We investigated the protective role of fish oil (FO-source of n-3 FA) enriched diet (in the first protocol) in 20 rats and FO administration intrarectally (in the second protocol) in 40 rats with trinitrobenzene (TNB) colitis. All colonic specimens were pathologically evaluated, myeloperoxidase enzyme activities were measured, leukotriene B4 (LTB4) and LTC4 levels were determined by radioimmunoassay. In the first protocol 10 rats (group A1) were fed with 8% sunflower and cotton oil enriched diet and (group A2) with 8% FO enriched diet for 6 weeks. At the end of this period, TNB (30 mg in 0.25 ml of 30% ethanol) were intrarectally administered. After 2 weeks, rats were sacrificed. MPO activities (2.47 versus 30.17), LTB4 (34.5 versus 903.3) and LTC4 (77.7 versus 456.0) levels were significantly reduced in group A2 compared with group A1 (P<0.005). There was also a significant difference in pathologic scores (1.55 versus 2.12, P<0.002) between two groups. In the first part of the second protocol, 20 male rats were randomized into two equal groups (B1 and B2) and TNB colitis was induced. After 1 day, 1 ml of saline (group B1) or n-3 FA enemas (group B2) were administered every day for 2 weeks. At the end of this period, rats were sacrificed and evaluated as done for previous groups. Although there was no significant difference between the two groups in comparison with MPO enzyme activities and pathologic scores, the LTB4 (130.1 versus 971.0) and LTC4 (126.0 versus 532.0) levels of FO group were significantly reduced (P<0.005). In the second part of the second protocol, 20 male rats were randomized into two groups. One millilitre of saline (group B3) or FO enemas (group B4) were administered to rats every day for 3 days. At the fourth day, TNB-colitis was induced and after 24 h rats were sacrificed. We could not find any significant difference in MPO activities, pathologic scores, LTB4 and LTC4 levels between groups B3 and B4. In conclusion, FO enriched diet decreased both pathologic damage and tissue LT levels. The second protocol of our study revealed that the long-term FO enemas decreased the LTB4 and LTC4 levels; however, did not have any beneficial effect on the tissue lesions. Short periods of FO enemas did not have a protective role in the occurrence of experimental colitis. The present study showed that FO enemas significantly decreased LT levels. The protective effect of FO (oral and enema) in TNB colitis may open a new insight into the treatment of inflammatory bowel disease.

Fatty acid composition and arachidonate metabolites in the livers of ethanol-treated rats fed an arachidonate-supplemented diet: effect of dietary fat.

The effects of 1% arachidonic acid ethyl ester (AA) administration on the liver prostanoid metabolites and on serum and liver lipids in 3 g/kg ethanol-administered rats fed 10% lard or corn oil were studied. The rats were divided into 6 groups: lard-sucrose (Lard-Suc); lard-ethanol without AA (Lard-Et); lard-ethanol with AA (Lard-EtAA); corn oil-sucrose (Corn-Suc); corn oil-ethanol without AA (Corn-Et); and corn oil-ethanol with AA (Corn-EtAA). Liver triglyceride increased in Corn-EtAA compared with Corn-Et. Arachidonic acid (20: 4n-6) levels in liver phospholipid were significantly decreased in Corn-Et, but elevated in Lard-Et. The levels of 20:4n-6 were significantly increased with AA administration in both ethanol groups. Liver 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in Corn-Suc (24.7 +/- 5.1 pg/mg protein) was markedly higher than in Lard-Suc (4.5 +/- 1.2 pg/mg protein), and the 6-keto-PGF1 alpha lowered significantly with the addition of ethanol (9.3 +/- 0.9 pg/mg protein), but it increased with AA administration (21.6 +/- 4.9 pg/mg protein). In Lard-EtAA, a significant increase in 6-keto-PGF1 alpha was observed compared with Lard-Suc. The liver leukotriene B4 (LTB4) level in Lard-Suc was significantly lower than that of Corn-Suc. In the corn oil group, ethanol feeding was associated with a significant increase in liver LTB4. AA administration to Corn-Et suppressed the elevated LTB4. Serum thiobarbituric acid-reactive substance (TBARS) concentrations in the corn oil group were higher than in the lard group, and these concentrations were not altered by AA administration. From these results, we concluded that the administration of AA in rats treated with ethanol increased 20:4n-6 in liver phospholipid and liver PGI2 levels, irrespective of dietary fat, and may protect against alcoholic liver injury. AA with a diet rich in linoleic acid (18:2n-6), however, may increase fat in the alcoholic liver.

Intranasal capsaicin is efficacious in non-allergic, non-infectious perennial rhinitis. A placebo-controlled study.

BACKGROUND: Several authors described capsaicin, the pungent substance in red pepper, as an efficacious therapy for non-allergic non-infectious perennial rhinitis (NANIPER). Repeated capsaicin application induces peptide depletion and specific degeneration of the unmyelinated sensory C-fibres in the nasal mucosa. METHODS: We performed a placebo-controlled (NaCl 0.9%) study with 25 NANIPER patients. Daily record charts and visual analogue scales (VAS) were used for clinical evaluation. Nasal lavages were obtained before, during, and after treatment. RESULTS: There was a significant and long-term reduction in the VAS scores in the capsaicin group. No significant difference was found between the placebo and capsaicin treated groups for the mean group concentrations of leukotriene (LT) C4/D4/E4, prostaglandin D2 (PGD2), and tryptase. The levels of mast cell mediators, tryptase and PGD2, and leukotrienes, mediators derived from a variety of inflammatory cells, were low at baseline and comparable with levels observed in nasal lavages obtained from normals. CONCLUSION: As involvement of inflammation could not be demonstrated, it is not surprising that capsaicin has no effect on inflammatory mediators. This suggests that inflammatory cells do not play a major part in the pathogenesis of NANIPER.

Antigen-specific sulphidoleukotriene production and histamine release in pollinic patients.

We studied sulphidoleukotriene (sLT) production, by means of CAST-ELISA (Bühlmann) in 92 atopic (54 pollinic and 38 non-pollinic) patients, and in 9 control subjects, after antigenic stimulation of peripheral blood leukocytes with 20 ng/ml and 2 ng/ml of Lolium perenne pollen extract, in the presence of IL-3. Antigen-specific stimulation of leukocytes from pollinic patients studied during the pollen season led to a sLT production significantly higher (p = 0.03 at 2 ng allergen/ml) than in those studied out of the pollen season. Histamine release was also significantly higher in pollen season than out of the season (p = 0.04 at 20 ng allergen/ml and p < 0.001 at 2 ng allergen/ml). There was a significant positive correlation between sLT production and histamine release (r = 0.67 at 2 ng allergen/ml and r = 0.57 at 20 ng/ml, both p < 0.001), and between sLT production and skin test results (r = 0.5 at 2 ng allergen/ml and r = 0.46 at 20 ng allergen/ml, both p < 0.001). We found that sLT production was lower, although not significantly, in patients older than 40 years, and histamine release was significantly (p = 0.02) higher in women than in men at 2 ng allergen/ml. We conclude that sLT production in pollinic patients is higher when antigenic pressure is increased in the environment, and that sLT quantification by CAST-ELISA might be useful for evaluation of this sensitization, with analogous results to the histamine release test.

Pustular psoriasis and aseptic purulent arthritis: possible role of leukotrienes B4 and C4 in a flare of synovitis.

BACKGROUND: Arthritis is a frequent complication of pustular psoriasis. However, the mechanism of onset of this arthritis still remains unclear. OBJECTIVES: The present study was conducted to determine whether leukotriene (LT) B4 or LTC4 is one of the proinflammatory mediators that possibly enhance exacerbation of the arthritis lesions. METHODS: We investigated the condition of the arthritis and autopsy findings of two cases of generalized pustular psoriasis with the severe complication of aseptic purulent arthritis. We also measured the synovial fluid levels of LTB4 and LTC4 by radioimmunoassay. RESULTS: The collected synovial fluid was purulent, but nonbacterial, and the synovium of the knee joint showed histopathologic evidence of polymorphonuclear leukocyte (PMN) invasion, edema and dilatation of small vessels showing similarity to a histologic reaction in the skin lesions. The immunoreactive (i-) LTB4 and i-LTC4 in the samples significantly exceeded the amount measured in osteoarthritis patients used as the controls. CONCLUSION: Thus, i-LTB4 and i-LTC4 appear to be generated in the arthritis lesions of pustular psoriasis, the former attracting PMNs to the joints and the latter causing exudation of synovial fluid.

Frequency of (n-3) polyunsaturated fatty acid consumption induces alterations in tissue lipid composition and eicosanoid synthesis in CD-1 mice.

This study assessed the effect of frequency of consumption of a diet containing 10 g fat/100 g, with a (n-3):(n-6) polyunsaturated fatty acid (PUFA) ratio of 0.5, on tissue fatty acid composition and eicosanoid synthesis in CD-1 mice. With greater (n-3) PUFA consumption frequency, hepatic and peritoneal cell (n-3) PUFA levels changed to 14.4 +/- 1.3 and 12.4 +/- 0.9 mol/100 mol, respectively, from 2.4 +/- 0.3 and 1.9 +/- 0.3 mol/100 mol in control animals consuming a diet without (n-3) PUFA. Hepatic and peritoneal cell (n-6) PUFA levels were reduced to 6.4 +/- 0.5 and 7.6 +/- 0.5 mol/100 mol, respectively, with daily (n-3) PUFA consumption, compared with 23.6 +/- 0.7 and 17.9 +/- 0.7 mol/100 mol in control animals. Prostaglandin E, 6-keto-prostaglandin F1 alpha, and 4-series sulfidopeptide leukotriene biosyntheses reflected frequency of (n-3) PUFA consumption, with daily (n-3) PUFA consumption reducing prostaglandin E, consumption of (n-3) PUFA every other day reducing 6-keto-prostaglandin F1 alpha, and (n-3) PUFA consumption every 3 d reducing leukotriene C4 and leukotriene E4. Leukotriene C5 and leukotriene E5 changed from undetectable in animals consuming the control diet to > 40% of total leukotriene production in animals consuming (n-3) PUFA daily. Daily to biweekly consumption of fish or fish oil [1.26-0.63 g/wk of (n-3) PUFA, 6-3% of energy] may be a means for changing eicosanoid production. Consumption of (n-3) PUFA less often than twice a week may not change eicosanoid synthesis.