The immune system* is a complex array of organs, tissues and specialized cells that protects us from outside invaders, such as bacteria, viruses, allergens and from harmful insiders, such as infected cells and toxins. Sometimes, the immune system turns on itself-hence the term autoimmune-damaging tissues and producing substances that generate chronic health conditions. Examples of autoimmune diseases include type 1 diabetes (insulin-dependent), multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. The body's handling of polyunsaturated fatty acids (PUFAs) is involved in each of these conditions.

One protective action of the immune system is inflammation, a response that fights bacteria and other infectious agents. But when inflammatory responses are excessive, as they are in asthma and rheumatoid arthritis, they result in redness, swelling, pain, stiffness and other symptoms. Inflammatory responses account for the wheeze and breathing difficulties in asthma, kidney inflammation in nephritis, itchiness of eczema, and the red wheals of insect bites and allergic dermatitis. Many medicines work by suppressing excessive inflammation.

Inflammation is characteristic of several chronic diseases such as atherosclerosis (clogged arteries). Inflammation develops in tissues such as blood vessel walls, lungs, and connective tissue partly through the activity of macrophages, cells that protect by scavenging unwanted particles, invading organisms and toxins (Figure 1). However, the hostile side of macrophage activity is the production of pro-inflammatory substances that worsen atherosclerosis.

Immune and inflammatory responses also underlie allergies, including those triggered by food and inhaled particles such as pollen and dust mites. Sensitive or allergic individuals react to harmless substances (allergens) by launching an immune response. For example, certain foods, pollen and dust mites can trigger allergic reactions. In allergic responses, the immune system produces large amounts of a particular antibody called IgE. Interaction of the allergen with IgE triggers a cascade of events resulting in allergic symptoms (Figure 2).

POLYUNSATURATED FATTY ACIDS IN INFLAMMATION

PUFAs are the precursors of substances that can promote or restrain inflammation. As a group, these chemicals are called eicosanoids. The most widespread eicosanoids are derived from arachidonic acid, an omega-6 PUFA. These eicosanoids stimulate blood clotting that can result in heart attack and stroke and they contribute to plaque formation in blood vessel walls. They also generate cytokines-mediators of inflammatory processes-that harm blood vessel walls. In the lungs and respiratory passages, another type of arachidonic acid-derived eicosanoid, leukotrienes, constrict the airway muscles making breathing more difficult. Leukotrienes can trigger asthma attacks. Anti-asthma drugs work by interfering with leukotriene activity.

The PUFAs found in fish oil, mainly EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) suppress and counter-act the activity of arachidonic acid-derived eicosanoids. EPA, in particular, competes with arachidonic acid for incorporation into cell membranes. Through this competition, it reduces the amount of arachidonic acid available for eicosanoid production. In addition, EPA generates its own type of eicosanoids that have less potent inflammatory activity
than those made from arachidonic acid.

Arachidonic acid also generates substances called lipoxins that work to stop inflammatory activity. This means that arachidonic acid is active in promoting and ending inflammatory responses. In a similar way, EPA also generates substances called "resolvins" that hasten the end of inflammation. Aspirin facilitates the production of lipoxins and resolvins. Thus, fish oil PUFAs oppose inflammatory activity through decreased production of inflammatory mediators, production of weaker eicosanoids and increased production of substances that halt inflammation. As a result they lessen the inflammatory symptoms of asthma, rheumatoid arthritis, atherosclerosis, inflammatory bowel disease and others. There is also some recent evidence that fish oil-derived resolvins are anti-inflammatory under conditions, such as severe gum disease, where lipoxins from arachidonic acid are not. These emerging findings suggest that fish oil PUFAs may have unique anti-inflammatory effects in certain disease conditions.

*Words in blue are described in the glossary.

* For more, see the government publication, "Understanding the Immune System: How It Works"