chronic inflammation with increased thromboxane a2 activity atherosclerosis stroke heart disease peripheral arterial disease infection aids erectile dysfunction chronic obstructive pulmonary disease asthma alzheimers cancer smoking obesity type 2 diabetes

Chronic inflammation is a distortion of a normal body response that is associated with the diseases of aging.

Internists, cardiologists, oncologists, and nutritionists continue to find evidence linking chronic inflammation with the diseases of aging. The effects of chronic inflammation accumulate over a lifetime to manifest themselves in a number of disorders, including heart disease, cancer, diabetes, pulmonary disease, arthritis, erectile dysfunction, and Alzheimer’s disease.

Chronic inflammation is poles apart from normal acute inflammation. Acute inflammation is the familiar beneficiary response of our healthy immune system to such stimuli as injury, infection, or shock. Chemicals called cytokines are released by our cells to trigger local reaction, including redness, heat, swelling, and pain. In acute inflammation, the cytokines trigger the immune, complement, kallikrein, and clotting systems, which cause discomfort but rapidly restore the body to health.

The failure of acute inflammation to “turn off” frequently is the beginning of chronic inflammation (also called silent, systematic, hidden, or low-grade inflammation). Chronic inflammation is frequently the result of our poor lifestyle, dietary, and nutritional choices as well as the environment that surrounds us. Over time, chronic inflammation has the ability to activate the genes we inherited, fueling chronic diseases.

The contribution of smoking and overeating to chronic inflammation is well known. Less recognized factors influencing chronic inflammation include:

  • Fat tissue is a source of cytokines
  • Certain foods provide inflammatory fats
  • Stress
  • Sleeping disorders
  • Chronic minor infections, such as gum disease, stomach ulcers, and upper respiratory infections

Chronic inflammation is the result of serious complex cellular reactions.

The thromboxane A2 pathway plays a major role in the development of chronic inflammation. Urinary 11-dehydrothromboxane B2 (Chronic Inflammation Test) is an indirect measure of thromboxane production. Two of the major components governing the thromboxane A2 pathway are arachidonic acid and Nuclear Factor kappa B.

Arachidonic Acid (Omega-6)

arachidonic acid

See the effects of nutrition on chronic inflammation and the role of arachidonic acid here.

Arachidonic acid, known as Omega-6 fatty acid, is a key metabolic source for inflammation. Arachidonic acid is the primary component of peanut oil, but is also produced from the transformation of other fatty acids by metabolism. How is arachidonic acid produced?

Fatty acids in the diet, such as linolenic acid, transform in the body to the gamma-linolenic acid (GLA) by the action of a cellular enzyme delta-6-desaturase. GLA rapidly converts to dihomo-gamma-linolenic acid (DGLA). DGLA produces many desirable eicosanoids with strong anti-inflammatory effects; however, DGLA is also the substrate for the delta-5-desaturase enzyme that produces arachidonic acid.

Arachidonic acid is converted by both platelet cyclooxygenase-1 (COX-1) and the inflammatory enzyme cyclooxygenase-2 (COX-2) into the powerful and dangerous thromboxane A2. Thromboxane A2 makes platelets sticky, leading to blood clots, and causes blood vessels to constrict, raising blood pressure. Thromboxane A2 rapidly converts in the blood to inactive thromboxane B2, which is metabolized by the liver to 11-dehydrothromboxane B2 (Chronic Inflammation Test) and is filtered by the kidneys into the urine.

Nuclear Factor kappa B (NFkB)

Nuclear Factor kappa B

NFkB transcription factors are located in an inactive form in the cytoplasm of our cells for the purpose of regulating immune and inflammatory responses. NFkB is a protein that functions as a switch to turn inflammation on and off in our bodies. An important role of NFkB is to induce and maintain the inflammatory state underlying metabolic and chronic diseases, including maintaining the balance of energy governing glycolysis and respiration.

NFkB is definitely one of the most important regulators of the pro-inflammatory expression of genes. NFkB is activated at inflammatory sites in many diseases where it is capable of inducing transcription of pro-inflammatory adhesion molecules, cytokines, chemokines, nitric oxide, and cyclooxygenase-2.

Cyclooxygenase-2 is the enzyme responsible for the formation of thromboxane A2 from arachidonic acid.

During the aging process, the expression of NFkB increases in our body, encouraging systemic chronic inflammation and turning on the genes for chronic diseases we have inherited. Scientists estimate more than 90 percent of chronic diseases are the direct result of chronic inflammation.

See the effects of environmental and external factors on chronic inflammation and the role of NFkB here.

Treating Chronic Inflammation?

The effectiveness of dietary and lifestyle improvements can be monitored using the chronic inflammation test.

thromboxane a2 suppression

Disclaimer:
Prescription drugs and integrative therapies used individually or in combination can have powerful effects. Initiation or change of any treatment must be under the direction of a licensed healthcare professional.

Dietary Omega-6 fatty acids, like arachidonic acid, initiate a cascade of events that end with inflammation. The Omega-3 fatty acids, eicosapentanoic acid (EPA) and dihomo-gamma-linolenic acid (DGLA), compete with arachidonic acid to reduce chronic inflammation. Reducing arachidonic acid and regulating its activity is essential to the prevention, control, or elimination of chronic inflammation.

Chronic inflammation may be prevented or reduced by selecting foods rich in EPA and DGLA that reduce arachidonic acid's production and effect. Diet may be enhanced with supplements, fish oil rich in Omega-3 fatty acids for example. Exercise can reduce production of cytokines that trigger arachidonic acid metabolism, and weight loss may reduce the number of cytokine-producing fat cells.

Dietary changes take time and discipline. Many integrative therapies have been shown to reduce cyclooxgyenase-2 activity.

In all cases, progress may be monitored in regular intervals using the Chronic Inflammation Test to measure 11-dehydrothromboxane B2.