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

In a longitudinal study of HIV seropositive patients, there were fluctuations in the specificity of cytotoxic T cells for the virus. This was matched by variability in proviral gag DNA epitope sequences in the lymphocytes of these patients. Some of these viral variants are not recognized by autologous T cells. Accumulation of such mutations in T-cell antigenic targets would provide a mechanism for immune escape.

Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition.

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.

Sequences of 234 complete genomes and 631 hepatitis B surface antigen genes were used to assess the worldwide diversity of hepatitis B virus (HBV). Apart from the described two subgenotypes each for A and F, also B, C, and D divided into four subgenotypes each in the analysis of complete genomes supported by significant bootstrap values. The subgenotypes of B and C differed in their geographical distribution, with B1 dominating in Japan, B2 in China and Vietnam, B3 confined to Indonesia, and B4 confined to Vietnam, all strains specifying subtype ayw1. Subgenotype C1 was common in Japan, Korea, and China; C2 in China, South-East Asia, and Bangladesh, and C3 in the Oceania comprising strains specifying adrq-, and C4 specifying ayw3 is encountered in Aborigines from Australia. This pattern of defined geographical distribution was less evident for D1-D4, where the subgenotypes were widely spread in Europe, Africa, and Asia, possibly due to their divergence having occurred a longer time ago than for genotypes B and C, with D4 being the first split and still the dominating subgenotype of D in the Oceania. The genetic diversity of HBV and the geographical distribution of its subgenotypes provide a tool to reconstruct the evolutionary history of HBV and may help to complement genetic data in the understanding of the evolution and past migrations of man.

Genetic Diversity of Hepatitis B Virus Strains Derived Worldwide: Genotypes, Subgenotypes, and HBsAg Subtypes

Among the many viruses that are known to infect the human liver, hepatitis B virus (HBV) and hepatitis C virus (HCV) are unique because of their prodigious capacity to cause persistent infection, cirrhosis, and liver cancer. HBV and HCV are noncytopathic viruses and, thus, immunologically mediated events play an important role in the pathogenesis and outcome of these infections. The adaptive immune response mediates virtually all of the liver disease associated with viral hepatitis. However, it is becoming increasingly clear that antigen-nonspecific inflammatory cells exacerbate cytotoxic T lymphocyte (CTL)-induced immunopathology and that platelets enhance the accumulation of CTLs in the liver. Chronic hepatitis is characterized by an inefficient T cell response unable to completely clear HBV or HCV from the liver, which consequently sustains continuous cycles of low-level cell destruction. Over long periods of time, recurrent immune-mediated liver damage contributes to the development of cirrhos...

G. Manzillo

Papers

Vaccine-induced escape mutant of hepatitis B virus

Hepatitis B variant in Europe.