calcimycin and eicosapentaenoic-acid-ethyl-ester

The effects of dietary supplementation with highly purified eicosapentaenoic acid ethyl ester (EPA-E) (MND-21) on asthma symptoms, fatty acids in serum, and generation of leukotriene (LT) C4, LTC5, LTB4 and LTB5 by leukocytes stimulated with calcium ionophore A23187 were studied in 10 patients with bronchial asthma. The patients received nine capsules of MND-21 (2.7 g EPA-E) each day for 12 weeks. Leukocytes obtained from 39 patients with asthma who did not receive EPA-E were used as the control. Fatty acid composition was evaluated by gas chromatography and LT generation was measured by reverse-phase high performance liquid chromatography. EPA-E increased EPA content more than threefold, without changing the quantities of arachidonic acid in serum lipids. Leukocytes obtained from patients given EPA-E for 4 weeks generated less LTC4 (53.5 +/- 23.3 ng/10(7) cells) and LTB4 (24.9 +/- 12.4 ng/10(7) cells) than did those from control patients (142.4 +/- 91.6 ng/10(7) cells and 58.3 +/- 34.8 ng/10(7) cells, respectively). Although significant levels of LTC5 and LTB5 were present after 4 weeks of EPA-E (6.5 +/- 1.9 ng/10(7) cells and 4.6 +/- 2.7 ng/10(7) cells, respectively), generation of total LTC (LTC4 + LTC5) and total LTB (LTB4 + LTB5) were substantially suppressed. Symptoms had improved after two months of EPA-E, but the effect was temporary. We conclude that in patients with asthma, treatment with EPA-E may attenuate leukocyte function without distinctly changing the severity of asthma.

Topics: Aged; Asthma; Calcimycin; Cells, Cultured; Eicosapentaenoic Acid; Female; Humans; Leukocytes; Leukotrienes; Male; Middle Aged

Sprague-Dawley rats were fed eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) ethyl esters at the 2% level for 3 weeks to clarify their effects on immune functions. In the rats fed EPA or DHA, serum cholesterol, triglyceride, and phospholipid (PL) levels were significantly lower than those in the rats fed safflower oil. In PL fractions of serum, liver, lung, splenocytes, and peritoneal exudate cells (PEC), increases in linoleic and dihomo-gamma-linolenic acid contents and a decrease in arachidonic acid (AA) content were observed in the rats fed EPA or DHA. In addition, the EPA content increased in the rats fed EPA and DHA. In the rats fed EPA or DHA, a decrease of LTB4 productivity and an increase of LTBs productivity were observed in the PEC, in response to the treatment with 5 microM calcium ionophore A23187 for 20 min. The changes in leukotriene production were more marked in EPA-fed rats than in DHA-fed rats. These results suggest that dietary EPA affects lipid metabolism and leukotriene synthesis more strongly than DHA.

Topics: Animals; Calcimycin; Dietary Supplements; Docosahexaenoic Acids; Eicosapentaenoic Acid; Exudates and Transudates; Fatty Acids; Immunoglobulins; Ionophores; Leukotriene B4; Lipid Metabolism; Lipids; Liver; Male; Phospholipids; Rats; Rats, Sprague-Dawley

The fatty acid composition of rat polymorphonuclear leukocytes (PMN) was modified by diets supplemented with a high linoleate (LA) safflower oil (76% LA), mixtures of eicosapentaenoate (EPA) and safflower oil (EPA(20) containing 20% EPA and 61% LA, EPA(40) containing 40% EPA and 46% LA), mixtures of docosahexaenoate (DHA) and safflower oil (DHA(20) containing 20% DHA and 61% LA, DHA(40) containing 40% DHA and 46% LA) or a high alpha-linolenate (alpha-LNA) perilla oil (57% alpha-LNA and 13% LA), and then lipid mediator production in casein-induced peritoneal PMN were compared. EPA and DHA were relatively ineffective in reducing platelet-activating factor (PAF) production; a statistically significant reduction was observed only in the DHA(40) group. In contrast, perilla oil reduced PAF production by 50% as compared with safflower oil. Arachidonate (AA) in the PAF precursor, 1-alkyl-2-acyl-glycerophosphocholine, was roughly correlated with PAF production, but EPA and DHA in the precursor lipid were relatively unrelated. On the other hand, both PGE2 and LTB4 production correlated positively with AA and negatively with EPA and DHA in PMN phospholipids; EPA tended to be somewhat more effective than DHA in reducing PGE2 and LTB4 formation; the activity of perilla oil was no less than EPA(20). Thus, replacing safflower oil with perilla oil was no less effective than supplementing safflower oil with EPA or DHA (at 40% of total fatty acids) in reducing lipid mediator production in rat PMN.

Topics: alpha-Linolenic Acid; Animals; Calcimycin; Dietary Fats, Unsaturated; Docosahexaenoic Acids; Eicosanoids; Eicosapentaenoic Acid; Ionophores; Linoleic Acid; Male; Neutrophils; Phospholipids; Plant Oils; Platelet Activating Factor; Rats; Rats, Sprague-Dawley; Safflower Oil