The term inflammation is derived from the Latin expression' to set on fire'.
Inflammation is a complex series of chemical events involving vascular tissue (blood vessels). Inflammation is the body’s response to harmful stimuli. It is an attempt to rid the body or contain an offensive agent.
Inflammation is classified as either acute or chronic.
Acute inflammation is the body’s initial response to 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. These are the cardinal signs of inflammation.
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 of inflammation; 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 and leukotrienes are the compounds 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 carbon units, is the starting point in the formation of the three inflammatory enablers.
Arachidonic acid, in addition can also be converted into cholesterol and from here on to any of the steroid hormones.
Both leukotrienes and prostaglandins are directly formed from arachidonic acid, while thromboxane must be formed from prostaglandins.
Inflammatory agents retain the 20-carbon skeleton of their parent compounds (arachidonic acid) giving rise to the name for thr entire family of compounds. Inflammatory agents are called eicosanoids (eicosa, Greek for the number 20).
The pathway that the arachidonic acid molecule follows is complex. It involves the enzyme cyclo-oxygenase, which exists in two forms and which catalyzes the reaction of arachidonic acid into prostaglandin.
In addition to the cyclo-oxygenase enzyme system, another enzyme, 5-lipoxygenase also acts on arachidonic acid to produce leukotrienes. Leukotrienes are found in the synovial fluid of joints.
Prostaglandins are eicosanoid mediators derived from arachidonic acid. Prostaglandins are produced in nearly all body tissues when cells are damaged. Prostaglandins or 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, 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, (amino acid chains). Prostaglandins are instead lipids, long chain fatty acids with small hydrophobic heads.
Prostaglandins and leukotrienes incite inflammation following exercise.
Reducing their production is one of the goals of this program.
One way is to reduce the amount of linoleic acid in the diet.
Leukotrienes are eicosanoid mediators, derived from arachidonic acid. Leukotrienes are responsible for the effects of asthma and allergies.
Leukotrienes cause the contraction of the smooth muscle tissue that lines the wall of blood vessels. They are also found in the bronchial passages of the lungs.
Leukotrienes stimulate leukocytes (while blood cells). Leukotrienes are produced by white blood cells and 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.
The lipoxygenase enzymes are found in both plant and animal cells.
In plants like 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.
Arachidonic Acid Destiny
Prostaglandins, thromboxanes and leukotrienes are chemically and metabolically related since they are all derived from the 20-carbon molecule, arachidonic acid. Arachidonic acid is a polyunsaturated fatty acid.
Cholesterol is another compound derived from arachidonic acid. The destiny of arachidonic acid has a profound effect on health.
Arachidonic acid is stored in cell membranes as part of its phospholipid structure. Here it can be found floating or embedded in the membrane itself. This provides the molecule with the ability to be easily and quickly dislodged and metabolized.
Arachidonic acid is released through the action of phospholipase A2. The subscript 2 denotes the number of double bonds in the fat chain and also indicates it leads to the formation of the 2 series of prostaglandins.
The 2 series of prostaglandins are the pro-inflammatory ones.
Arachidonic acid is derived from the dietary oil, linoleic acid, an omega-6 fatty acid.
Linoleic acid is found in vegetable oils.
Linoleic acid is an 18 carbon-chained omega-6 fatty acid. When linoleic acid is metabolized, it is converted into arachidonic acid. This conversion increases the fatty acid chain length by two carbons. By going from an 18 carbon base to a twenty allows the linoleic acid to be stored as arachidonic acid in the cell membrane, where it can be quickly released and converted into an enabler of inflammation or cholesterol.
Prostaglandins and the other inflammatory mediators are all derived from the polyunsaturated fatty acid, arachidonic acid.
Arachidonic acid is derived from the dietary fat, linoleic acid. The more linoleic acid in the diet, the more arachidonic acid becomes stored in cell membranes. The more arachidonic acid is stored, the more it can be converted into an enabler of Inflammation.
The conversion of linoleic acid to arachidonic acid is accelerated when the ratio of omega-6 fats to omega-3 is high.
Conversely, when there is high omega-3 concentration, this conversion is repressed and inflammation is minimized. The destiny of arachidonic acid is thus critical to repressing Inflammation and recovery following exercise.
Regulating the amount and type fat in the diet prevents inflammation and disease and speeds healing.
This strategy depends on replacing linoleic acid with olive oil and supplementing the diet with omega-3 fats. This favorably alters the lipid or cholesterol profile and improves the body’s omega fatty acid ratio.
A favorable ratio (high omega-3 levels) maintains arachidonic acid in its embedded form as part of the phospholipids in the membrane. Keeping them in this form, rather than free to be converted into inflammatory mediators, reduces inflammation.
Prostaglandins and thromboxanes arise from a series of chemical reactions that utilize the cyclooxygenase pathway.
Leukotrienes follow the lipoxygenase pathway, which leads to the production of protective mucus but is also responsible for allergic of anaphylactic attacks..