Inflammation

The term inflammation is derived from Latin and means to set on fire.

The classic signs of redness, swelling, and pain reflect the molecular turbulence of the tissues involved.

 

When inflammation occurs, the body's response is to prepare for the worst and respond accordingly. In fact, much of the damage done from an injury is on account of the body's response, not the actual injury.

Human neuronal chemistry treats both lack of food and injury as mortal enemies.

To deal with these perceived dangers, the body evolved complicated sytems to store excess calories as fat to prevent starvation. It also gave inflammation the role of sealing off the area to limit damage.

On the molecular level, inflammation is a complex series of chemical events within vascular tissue (blood vessels). The players involved are blood cells, which hsve sophisticated cascading mechanisms.

 Inflammation is the body’s response to harmful stimuli. It is an attempt to wall off the problem until it can rid itself of the offending agent.

 Inflammation is classified as either acute or chronic.

 Acute inflammation is the body’s initial response to the harmful stimuli. During this phase of inflammation, there is an increased movement of plasma and leukocyte cells from the blood to the injured tissues.  Acute inflammation is characterized by swelling, redness, pain, heat, and loss of function

 Prolonged inflammation or chronic inflammation is the continual destruction and repair of tissue. During this phase, there is a progressive shift in the type of cells (monocytes, macrophages), which migrate to the site of inflammation. Chronic inflammation is characterized by simultaneous destruction and healing of tissue.

There are three powerful inflammatory agents, prostaglandins, thromboxanes and leukotrienes. These chemical mediators stimulate the body’s inflammatory response.

Prostaglandins and leukotrienes are the enablers of inflammation. Prostaglandins are also known as prostanoids..

Prostaglandins cause inflammatory cell migration to injured joints.

Leukotrienes are responsible for mucus production during asthma attacks and inflammation in joints.

Thromboxanes are involved with clot formation.

 Arachidonic acid, a fatty acid chain of 20 carbons, is the starting point in the formation of the three inflammatory enablers.

Arachidonic acid can also be converted into cholesterol and then on to any of the steroid hormones.

Arachidonic acid stands at the crossroads of health. The fate and destination of arachidonic acid determines the manner in which the body reponds to stress and inflammation.

Both leukotrienes and prostaglandins are directly formed from arachidonic acid, while thromboxane must go through prostaglandin.

 

Inflammatory agents retain the 20-carbon skeleton of their parent compound (arachidonic acid).  For that reason the entire family of compounds are known as eicosanoids (eicosa is Greek for the number 20).

 

The pathways that arachidonic acid molecule follow are complex. It involves the enzyme cyclooxygenase, an enzyme that exists in two forms and which catalyzes the reaction of arachidonic acid into prostaglandin. The function of these enzymes is to regulate the inflammatory response

Besides the cyclooxygenase enzyme system, another enzyme, (5-lipoxygenase) can convert arachidonic acid when the body is in need of leukotrienes.

Leukotrienes are found in the synovial fluid of joints.

Prostaglandins

Prostaglandins are eicosanoid mediators, derived from arachidonic acid. Prostaglandins are produced in nearly all body tissues when their cells are damaged.

 

Prostanoids function as hormones but unlike hormones, only act at the site where they are produced.

 

Prostaglandins act as short-lived and short-range hormones.

 

The first of the prostaglandin compounds or prostanoids to be identified and studied was prostaglandin, so named because it was first isolated from the prostate glands of sheep. Prostaglandin was found to have a broad range of activities with roles in inflammation, cell division, migration and muscle tone. Prostaglandin was only the first of many such substances to be isolated and described.

 

Another compound was found to be particularly potent in causing the contraction of the smooth muscle tissue that sheaths blood vessels and the bronchial passages to the lungs.  This compound turned out not to be a single factor but rather a mixture of closely related molecules and were called leukotrienes. They were so named because of their ability to stimulate leukocytes (while blood cells).

 

 

Prostaglandins and leukotrienes are neither steroids (steroids requires a tetracyclic nucleus) nor proteins, which are made up of amino acid chains.

 

Prostaglandins are instead lipids, long chain fatty acids tails and a small hydrophobic head.

 

Prostaglandins and leukotrienes incite inflammation following exercise. Reducing their production is one of the goals of this program, which can be achieved by reducing the amount of linoleic acid in the diet..

 

 


 

Leukotrienes are eicosanoid compounds, derived from the body’s store of arachidonic acid. Leukotrienes are responsible for the effects of asthma and allergies.

 

Leukotrienes cause the contraction of the smooth muscle tissue that sheath and line the walls of blood vessels. They are also found in bronchial passages of the lungs.

 

Leukotrienes are produced by leukocytes (while blood cells). These 20 carbon long compounds bind to receptors on smooth muscles. Leukotrienes are powerful contractors of smooth muscle.

Contraction of smooth muscle in blood vessels produces vasoconstriction. Contraction of smooth muscle in the lungs produce bronchoconstriction.  Leukotrienes thus play an important role in anaphylactic (allergic) reactions.

 

Leukotrienes are neither steroids nor proteins but instead are lipids. Lipids are made up of a long chain  fatty acid  tail and a small hydrophobic head.

Leukotriene formation begins with a peroxidation reaction catalyzed by 5-lipoxygenase with subsequent steps involving glutathione, a powerful antioxidant enzyme.

Lipoxygenase enzymes are found in both plant and animal cells. In plants, such as soybeans, the lipoxygenase enzyme is used for the synthesis of antimicrobial compounds.  This may explain why soy products are so healthy.

Human lipoxygenase on the other hand, is an iron-based enzyme that catalyzes the oxidation of arachidonic acid and causes the anaphylactic effects described above.

 

Lipoxygenase is capable of binding arachidonic acid with molecular oxygen causing the formation of hydroperoxide radicals and eicosanoic acids.

Further dehydration of these radicals results in the production of four types of leukotrienes. The reactions occur in white blood cells, macrophages and platelets.