Reductions in dietary fat, saturated fat, and cholesterol have been recommended to reduce the risk of heart disease in our society. The effects of these modifications on human cytokine production and immune responses have not been well studied. 22 subjects > 40 yr of age were fed a diet approximating that of the current American (14.1% of calories as saturated fatty acids, ISFAJ, 14.5% monounsaturated fatty acids [MUFAJ, 6.1% [n-61 polyunsaturated fatty acids IPUFAJ, 0.8% In-31 PUFA, and 147 mg cholesterol/ 1,000 calories) for 6 wk., after which time they consumed (11 in each group) one of the two low-fat, low-cholesterol, high-PUFA diets based on National Cholesterol Education Panel (NCEP) Step 2 recommendations (4.04.5% SFA, 10.8-11.6% MUFA, 10.3-10.5% PUFA, 45-61 mg cholesterol /1,000 calories) for 24 wk. One of the NCEP Step 2 diets was enriched in fish-derived (n-3) PUFA (low-fat, high-fish: 0.54% or 1.23 g/d eicosapentaenoic acid IEPAI and docosahexaenoic acid IDHAI 1121-188 g fish/di) and the other low in fish-derived (n-3) PUFA (low-fat, low-fish 10.13% or 0.27 g/d EPA and DHAJ 133 g fish/di). Measurements of in vivo and in vitro indexes of immune responses were taken after each dietary period. Long-term feeding of low-fat, lowfish diet enriched in plant-derived PUFA increased blood mononuclear cell mitogenic response to the T cell mitogen Con A, IL-1#,, and TNF production and had no effect on delayed-type hypersensitivity skin response, IL-6, GM-CSF, or PGE2 production. In contrast, the low-fat, high-fish diet significantly decreased the percentage of helper T cells whereas the percentage of suppressor T cells increased. Mitogenic responses to Con A and delayed-type hypersensitivity skin response as well as the production of cytokines IL-1ft, TNF, and IL-6 by mononuclear cells were significantly reduced after the consumption of the low-fat, high-fish diet (24, 40,45,35, and 34%, respectively; P < 0.05 by two-tailed Student's t test except for IL-1,6 and TNF, which is by one-tailed t test). Our data are consistent with the concept that the NCEP Step 2 diet that is high in fish significantly decreases various parameters of the immune response in contrast to this diet when it is low in fish. Such alterations may be beneficial for the prevention and treatment of atherosclerotic and inflammatory diseases but may be detrimental with Address reprint requests to Simin Nikbin Meydani, DVM, PhD, Nutri-

The anorexia associated with acute and chronic inflammatory or infectious conditions is poorly understood. Our objectives were to explore the anorexigenic effects of interleukin-1 (IL-1) in the rat. Recombinant human (rh) IL-1,6, murine (rm) IL-la and to a lesser extent rhIL-la significantly reduced food intake at 24.0 gg/kg i.p. but not at lower doses, in young (200-250 g) meal-fed rats on chow diets. The anorexic effect appears to be mediated by prostaglandins since pretreatment with ibuprofen completely blocked it, and a fish oil based diet abolished it, in comparison to corn oil or chow diets. Fish oil feeding also decreased basal and IL-1 stimulated prostaglandin E2 production by tissues in vitro (liver, brain, peritoneal macrophages) and in the whole body. Constant intravenous infusions of lower doses of IL-1 also diminished food intake, though intravenous boluses did not (reflecting rapid renal clearance). Chronic daily administration of IL-1 caused persistent inhibition of food intake for 7-17 d in chow and corn oil fed rats, but had no effect in fish oil fed rats. There was an attenuation of the effect (tachyphylaxis) after 7 d in corn oil and chow fed rats, but slowed weight gain and lower final weights were observed after 17-32 d of daily IL-1. Old (18-20 mo Fisher 344) rats showed less sensitivity to IL-1 induced anorexia. In conclusion, IL-1 is anorexigenic in the rat, but this is influenced by the structural form of IL-1, the route and chronicity of administration, the source of dietary fat, and the age of the animal. The ability of prior fat intake to influence the anorexic response to IL-1 represents a novel nutrient-nutrient interaction with potential therapeutic implications.

This review of corn oil provides a scientific assessment of the current knowledge of its contribution to the American diet. Refined corn oil is composed of 99% triacylglycerols with polyunsaturated fatty acid (PUFA) 59%, monounsaturated fatty acid 24%, and saturated fatty acid (SFA) 13%. The PUFA is linoleic acid (C18:2n-6) primarily, with a small amount of linolenic acid (C18:3n-3) giving a n-6/n-3 ratio of 83. Corn oil contains a significant amount of ubiquinone and high amounts of alpha- and gamma-tocopherols (vitamin E) that protect it from oxidative rancidity. It has good sensory qualities for use as a salad and cooking oil. Corn oil is highly digestible and provides energy and essential fatty acids (EFA). Linoleic acid is a dietary essential that is necessary for integrity of the skin, cell membranes, the immune system, and for synthesis of icosanoids. Icosanoids are necessary for reproductive, cardiovascular, renal, and gastrointestinal functions and resistance to disease. Corn oil is a highly effective food oil for lowering serum cholesterol. Because of its low content of SFAs which raises cholesterol and its high content of PUFAs which lowers cholesterol, consumption of corn oil can replace SFAs with PUFAs, and the combination is more effective in lowering cholesterol than simple reduction of SFA. PUFA primarily lowers low-density-lipoprotein cholesterol (LDL-C) which is atherogenic. Research shows that PUFA has little effect on high-density-lipoprotein cholesterol (HDL-C) which is protective against atherosclerosis. PUFA generally improves the ratio of LDL-C to HDL-C. Studies in animals show that PUFA is required for the growth of cancers; the amount required is considered to be greater than that which satisfies the EFA requirement of the host. At this time there is no indication from epidemiological studies that PUFA intake is associated with increased risk of breast or colon cancer, which have been suggested to be promoted by high-fat diets in humans. Recommendations for minimum PUFA intake to prevent gross EFA deficiency are about 3% of energy (en%). Recommendations for prevention of heart disease are 8-10 en%. Consumption of PUFA in the United States is 5-7 en%. The use of corn oil to contribute to a PUFA intake of 10 en% in the diet would be beneficial to heart health. No single source of salad or cooking oil provides an optimum fatty acid (FA) composition. Many questions remain to be answered about the relation of FA composition of the diet to various physiological functions and disease processes.

The effect of marine- and plant-derived n-3 polyunsaturated fatty acids (PUFAs) on T cell-mediated immune response was studied in cynomolgus monkeys. Animals were first fed a 14-wk baseline diet; 10 animals were then fed diets containing 1.3% or 3.3% of energy as eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) which the other 10 were fed diets containing 3.5% or 5.3% of energy as alpha-linolenic acid (ALA) for two consecutive 14-wk periods. Both diets significantly decreased the percentage of T cells (except 1.3% EPA + DHA), T helper cells (except 1.3% EPA + DHA and 3.5% ALA), and T suppressor cells. Proliferative response of lymphocytes to T cell mitogens significantly increased after the diet containing 3.3% EPA + DHA. Interleukin 2 production significantly increased after the diets containing 1.3% and 3.3% EPA + DHA. No significant changes in mitogenic response or interleukin 2 production were found after ALA diets. Feeding 1.3% or 3.3% EPA + DHA or 5.3% ALA significantly suppressed prostaglandin E2 production in response to T cell mitogens. Plasma tocopherol concentrations were decreased significantly only in monkeys fed ALA diets. We conclude that after adjustment for the tocopherol concentration, marine-derived n-3 PUFAs but not plant-derived n-3 PUFAs increased T cell-mediated mitogenic response and interleukin 2 production. This is most likely due to diet-induced quantitative differences in cellular fatty acid composition and, thus, in prostaglandin E2 production and tocopherol status.

No abstract

Several recent reports have shown that diets in which the only source of fat was fish oil can modify the course of diseases with an inflammatory or immune component. In these experiments we examined the effect of a fish oil diet on experimental amyloidosis in mice. In most azocasein-treated mice, amyloid deposits were found in the spleen, varying from a trace to wide and contiguous perifollicular bands. The spleens of mice receiving fish oil had significantly less amyloid than did spleens of mice fed corn oil. A marked increase in spontaneous blastogenesis that occurred in azocasein-treated mice on corn oil was suppressed in azocasein-treated mice on fish oil. Substitution of the unsaturated fatty acids of corn oil with those of fish oil was also found to modify the prostaglandin profile of macrophages. This altered profile may change cellular immune function and/or enhance the processing of serum amyloid A to retard the induction of secondary amyloidosis in mice.