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Research Newsletter-Spring/Summer 2007

Two Faces of Inflammation

Victoria J. Drake, Ph.D.
LPI Research Associate

What is inflammation?

Inflammation is the immune response of tissues due to bodily injury. Clinical characteristics of acute inflammation include pain, heat, swelling, and redness at the site of the injury. Inflammation may also involve loss of function of the involved tissues. This type of acute inflammation is normally a localized, protective response following trauma or infection. However, if the agent causing the inflammation persists for a prolonged period of time, the inflammation becomes chronic. Chronic inflammation can result from a viral or microbial infection, environmental antigen (e.g., pollen), autoimmune reaction, or persistent activation of inflammatory molecules.

The inflammatory process involves a complex biological cascade of molecular and cellular signals that alter physiological responses, ultimately resulting in the familiar clinical symptoms. At the site of the injury, cells release molecular signals that cause a number of changes in the affected area: dilation of blood vessels, increased blood flow, increased vascular permeability, exudation of fluids containing proteins like immunoglobulins (antibodies), and invasion by leukocytes (white blood cells). Several different types of leukocytes, including granulocytes, monocytes, and lymphocytes, are involved in the inflammatory cascade. The cellular mediators of acute and chronic inflammation differ somewhat and are discussed below.

How does acute inflammation differ from chronic inflammation?

Acute Inflammation

Acute inflammation is a normal process that protects and heals the body following physical injury or infection. Acute inflammation involves local dilation of blood vessels as well as increased vessel permeability to improve blood flow to the injured area. At the site of an infection or injury, mast cells, platelets, nerve endings, endothelial cells, and other resident cells release signaling molecules and chemoattractants that recruit leukocytes to the affected area. Neutrophils, a type of granulocyte, are the first leukocytes to appear at the injured site. These cells phagocytose (engulf) and kill invading microorganisms through the release of non-specific toxins, such as superoxide radicals, hypochlorite, and hydroxyl radicals; these reactive oxygen species (ROS) kill pathogens as well as adjacent cells, sick and healthy alike. Neutrophils also release cytokines, including interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-alpha, gamma interferon (INF-gamma), and others. Such pro-inflammatory cytokines in turn induce the liver to synthesize various acute phase reactant proteins and also induce systemic inflammatory responses (e.g., fever and leukocytosis—a rise in the number of white blood cells). Neutrophils are short-lived and are thus primarily involved in the early stages of inflammation.

Chronic Inflammation

If the stimulus persists, inflammation can last days, months, and even years. Chronic inflammation is primarily mediated by monocytes and long-lived macrophages; monocytes mature into macrophages once they leave the bloodstream and enter tissues. Macrophages engulf and digest microorganisms, foreign invaders, and senescent cells. Macrophages release several different chemical mediators, including IL-1, TNF-alpha, and prostaglandins, that perpetuate the pro-inflammatory response. At later stages, other cells, including lymphocytes, invade the affected tissues: T lymphocytes kill virus-infected cells and B lymphocytes produce antibodies that specifically target the invading microorganisms for destruction.

Macrophages and other leukocytes release ROS and proteases that destroy the source of inflammation; however, damage to the body's own tissues often results. In fact, tissue damage is a hallmark of chronic inflammation. Another characteristic of chronic inflammation is repair of the damaged tissue by replacement with cells of the same type or with fibrous connective tissue. An important part of the inflammatory process involves local angiogenesis—the development of new blood vessels. In some instances, the body is unable to repair tissue damage, and the inflammatory cascade continues. Chronic inflammation is abnormal and does not benefit the body; in fact, chronic inflammation is involved in a number of disease states (see below).

Are specific tissues or organs especially vulnerable to the effects of inflammation?

Tissue damage that occurs during the inflammatory response must be actively repaired. Repair capabilities of the tissues within the body vary greatly because the cells have different regenerative abilities. For instance, cells with little to no regenerative capacity include neurons, cardiac cells, and skeletal muscle cells. Tissues comprised of these cells would be especially vulnerable to effects of inflammation. In contrast, skin cells are labile because they continue to proliferate throughout life; thus, wounds to the skin are often easily healed.

How is inflammation detected?

The inflammatory response involves countless mediators, some of which are used as clinical markers of inflammation or inflammatory diseases. The table below lists a few commonly used biomarkers of systemic inflammation. C-reactive protein (CRP), an acute-phase reactant protein synthesized in the liver, is the prototypic clinical biomarker of cardiac-related inflammation and is also a general marker of inflammation. Clinically, the most common tests to diagnose inflammation include measuring erythrocyte sedimentation rate (ESR), white blood cell count, and albumin levels. High ESR, high white cell counts, and low albumin are markers of inflammation. All of these tests are nonspecific; that is, an abnormal result might result from a condition unrelated to inflammation. Various cytokines and adhesion molecules are not often used in clinical settings primarily because such tests would not identify the source of inflammation within the body. However, such biomarkers are frequently used in basic scientific studies to investigate the cellular and molecular processes involved in the pathogenesis of inflammation-related diseases.


What diseases are associated with inflammation?

Several human diseases are inflammatory in nature, including asthma, Crohn's disease, rheumatoid arthritis, polymyalgia rheumatica, tendonitis, bursitis, laryngitis, gingivitis, gastritis, otitis, celiac disease (gluten intolerance), diverticulitis (infection of the diverticula in the colon), and inflammatory bowel disease. Additionally, a number of chronic diseases have inflammatory components, such as atherosclerosis, obesity, diabetes, cancer, and perhaps even Alzheimer's disease. The causes of several of these diseases are unknown, and the role of inflammation in disease pathogenesis is under investigation. For instance, it is known that adipose tissue secretes several inflammatory factors (adipocytokines) and that obesity is associated with macrophage infiltration in adipose tissue; however, the exact role of inflammation in the pathogenesis of obesity is currently unknown.

What dietary and lifestyle interventions may be useful to decrease inflammation?

Dietary components may modulate inflammatory responses within the body (see the table below). Overall, studies suggest that diets rich in saturated fats, trans fats (hydrogenated or partially hydrogenated oils), and high glycemic index foods stimulate inflammation. In contrast, adherence to a Mediterranean-style diet has been shown to reduce inflammation. A Mediterranean-style diet is rich in monounsaturated fatty acids from olive oil, fruits and vegetables, nuts, beans, and whole grains. In addition, a Mediterranean-style diet emphasizes consuming alcohol in moderation. Moderate alcohol consumption has been associated with a reduction in inflammation.

Essential fatty acids play a role in the body's inflammatory processes. Increasing dietary intake of the omega-3 fatty acids found in oily fish and fish oils—eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)—generally decreases several markers of inflammation, whereas increasing dietary intake of omega-6 fatty acids increases inflammatory markers. The ratio of omega-6 to omega-3 fatty acids in the typical Western diet is about 16:1, yet it is estimated that humans evolved on a diet with an omega-6 to omega-3 fatty acid ratio of about 1:1. Decreasing this ratio will likely reduce the prevalence and severity of various inflammatory conditions observed in Western societies.

Particular vitamins, minerals, and phytochemicals may also have therapeutic benefit in inflammatory diseases, but efficacy might depend on the specific disease state. A few reports suggest that the spices turmeric (curcumin) and ginger, as well as the herb Boswellia serrata, may inhibit the pro-inflammatory lipooxygenase or cyclooxygenase pathways; however, scientific data supporting anti-inflammatory properties are largely lacking. Catechins, polyphenolic compounds found in tea, have both antioxidant and anti-inflammatory effects. Further, data from animal models suggest that alpha-lipoic acid, when provided as a dietary supplement, has anti-inflammatory properties.

In addition to specific dietary components, achieving or maintaining a healthy body weight is important to prevent or control chronic inflammatory diseases. For instance, elevated CRP levels have been linked to obesity, and weight loss has been shown to decrease CRP levels. Weight loss most consistently results from both reducing daily caloric intake and increasing physical activity. Animal and human studies have found that various forms of exercise decrease both acute and chronic inflammation, as measured by reductions in CRP and particular cytokines. Furthermore, smoking cessation has been reported to decrease CRP, fibrinogen, and white blood cell count—all biomarkers of inflammation.


Are non-steroidal anti-inflammatory drugs (NSAIDs) considered safe?

NSAIDs like aspirin and ibuprofen are commonly used to relieve pain and control inflammation. Most NSAIDs nonspecifically inhibit one or more isoforms of cyclooxygenase (COX), an enzyme that catalyzes the formation of pro-inflammatory prostaglandins and thromboxanes. It is thought that the nonselective nature of NSAIDs causes adverse upper gastrointestinal effects in some regular NSAID users. Also, because NSAIDs inhibit thromboxanes, users experience decreased blood clotting ability, which could have clinical significance (e.g., increased risk of hemorrhagic stroke). Further, use of COX-2 specific NSAIDs, such as Celebrex and Vioxx, may have low gastrointestinal risks, but studies indicate increased risk of cardiovascular events with use of these drugs. Use of any type of NSAIDs should be closely supervised by a medical provider who examines the potential risks as well as therapeutic benefits.

Last updated May 2007

For more information about nutrition and inflammation, see the article in the Micronutrient Information Center.