Among the fatty acids, it is the omega-3 polyunsaturated fatty acids (PUFA) which possess the most potent immunomodulatory activities, and among the omega-3 PUFA, those from fish oil— eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)—are more biologically potent than -linolenic acid (ALA). Some of the effects of omega-3 PUFA are brought about by modulation of the amount and types of eicosanoids made, and other effects are elicited by eicosanoid-independent mechanisms, including actions upon intracellular signaling pathways, transcription factor activity and gene expression. Animal experiments and clinical intervention studies indicate that omega-3 fatty acids have anti-inflammatory properties and, therefore, might be useful in the management of inflammatory and autoimmune diseases. Coronary heart disease, major depression, aging and cancer are characterized by an increased level of interleukin 1 (IL-1), a proinflammatory cytokine. Similarly, arthritis, Crohn’s disease, ulcerative colitis and lupus erythematosis are autoimmune diseases characterized by a high level of IL-1 and the proinflammatory leukotriene LTB4 produced by omega-6 fatty acids. There have been a number of clinical trials assessing the benefits of dietary supplementation with fish oils in several inflammatory and autoimmune diseases in humans, including rheumatoid arthritis, Crohn’s disease, ulcerative colitis, psoriasis, lupus erythematosus, multiple sclerosis and migraine headaches. Many of the placebocontrolled trials of fish oil in chronic inflammatory diseases reveal significant benefit, including decreased disease activity and a lowered use of anti-inflammatory drugs. Key teaching points:  In Western diets, omega-6 fatty acids are the predominant polyunsaturated fats. The omega-6 and omega-3 fatty acids are metabolically distinct and have opposing physiologic functions.  Eicosapentaenoic acid (EPA) is released to compete with arachidonic acid (AA) for enzymatic metabolism inducing the production of less inflammatory and chemotactic derivatives.  Animal and human studies support the hypothesis that omega-3 PUFA suppress cell mediated immune responses.  In experimental animals and humans, serum PUFA levels predict the response of proinflammatory cytokines to psychologic stress. Imbalance in the omega-6/omega-3 PUFA ratio in major depression may be related to the increased production of proinflammatory cytokines and eicosanoids in that illness.  The increased omega-6/omega-3 ratio in Western diets most likely contributes to an increased incidence of cardiovascular disease and inflammatory disorders.  Patients with autoimmune diseases, such as rheumatoid arthritis, inflammatory bowel disease and asthma, usually respond to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation by decreasing the elevated levels of cytokines.

Omega-3 Fatty Acids in Inflammation and Autoimmune Diseases

During the past several decades, reduction in fat intake has been the main focus of national dietary recommendations to decrease risk of coronary heart disease (CHD). Several lines of evidence, however, have indicated that types of fat have a more important role in determining risk of CHD than total amount of fat in the diet. Metabolic studies have long established that the type of fat, but not total amount of fat, predicts serum cholesterol levels. In addition, results from epidemiologic studies and controlled clinical trials have indicated that replacing saturated fat with unsaturated fat is more effective in lowering risk of CHD than simply reducing total fat consumption. Moreover, prospective cohort studies and secondary prevention trials have provided strong evidence that an increasing intake of n-3 fatty acids from fish or plant sources substantially lowers risk of cardiovascular mortality. In this article, we review evidence from epidemiologic studies and dietary intervention trials addressing the relationship between dietary fat intake and risk of CHD, with a particular emphasis on different major types of fat, n-3 fatty acids and the optimal balance between n-3 and n-6 fatty acids. We also discuss the implications of the available evidence in the context of current dietary recommendations.

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Types of dietary fat and risk of coronary heart disease: a critical review.

Hepatitis B vaccines.

Fatty acid modulation of endothelial activation

Acute and chronic hepatitis B virus (HBV) infection is a leading cause of liver disease worldwide. It is estimated that approximately 350 million people worldwide have chronic HBV infection and that 1 million persons die each year from HBV-related chronic liver disease. In the past decade, significant progress in the understanding of the molecular virology and pathogenesis of HBV infection has been made. In addition, effective treatment modalities have been developed for persons with chronic infection. Worldwide, prevention of HBV transmission has become a high priority. In 1992, the Global Advisory Group to the World Health Organization recommended that all countries integrate hepatitis B vaccine into national immunization programs by 1997. Currently, 80 countries have done so and several others are planning to. Many countries have reported dramatic reductions in the prevalence of chronic HBV infection among children born since the hepatitis B vaccine was introduced into infant immunization schedules. Recent reports from Taiwan indicate a reduction in the incidence of liver cancer among children as a result of widespread hepatitis B vaccination programs.

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G. Maio

Papers

Hepatitis B variant in Europe.