Interleukins

The regulation of vital physiological processes, for example, replenishment of mature blood cells from bone marrow stem cells, termed hematopoiesis, and the activation of defense mechanisms against pathological microbes and injury has been shown to depend on the production and action of a variety of biologically active proteins, collectively known as cytokines. Central among cytokines is a class of mediators, largely involved in the regulation of immune, inflammatory, and hematopoietic functions, called the interleukins. They are produced mainly by leukocytes and act locally on other leukocytes in surrounding tissues. Each interleukin, of which there are now 29 designated ones, has a spectrum of biological activities via specific cell surface receptors. The 29 known interleukins can be clustered into three groups: noxious (the “bad,” eight members), comprising IL-1, IL-2, IL-6, IL-7, IL-8, IL-15, IL-17, and IL-18; protective (the “good,” five members), comprising IL-4, IL-10, IL-11, IL-12, and IL-13; and “aloof,” comprising IL-5, IL-9, IL-14, IL-16, and IL-19 through IL-29 (15 members).

Obesity is known to give rise to a number of inflammatory conditions in the body that are known to cause other disease conditions such as Type 2 diabetes, hypertension, arthritis, and so forth. In obesity, there is a marked rise in the amount of adipose tissue in the body. Historically, it was believed that adipose tissue consisted only of adipocytes or fat cells that were the sole sites of synthesis and storage of lipid. However, it has now been established that the adipocyte cells also contain a large number of other cells such as the fibroblasts, mast cells, macrophages, leukocytes, and other cells involved with inflammation. A marked increase of various cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, [Page 409]and so forth, are seen among the obese individuals. The five interleukins that have an increased production in obesity are briefly mentioned below:

• 1.
  IL-1β: along with TNF-α, IL-1β is considered a proinflammatory (causing inflammation) cytokine. The release of IL-1β is 50 percent higher in tissues of obese individuals. Both TNF-α and IL1-β modulate the release of other cytokines such as IL-6 and IL-8 in the adipocytes.
• 2.
  IL-6: This cytokine has been known to play a key role in the development of coronary heart disease. It is associated with the stimulation and release of some specialized proteins in the liver called the acute phase proteins. These proteins increase production of other markers of inflammation such as the C-reactive protein (CRP) by 10- to 100-folds. Enormous amounts of IL-6 are released by the human fat cells which then pass into the bloodstream and reach the liver. Higher amounts of circulating IL-6 in the blood stream and the liver are associated with insulin resistance, a cause of Type 2 diabetes. However, IL-6 is not associated with insulin action; it only stimulates the formation of anti-insulin factors.
• 3.
  IL-8: It is an interleukin that belongs to an ever-expanding family of proteins that exert chemoattractant activity to leukocytes and fibroblasts. This family of proteins is termed the chemokines. IL-8 is produced by monocytes, neutrophils, and NK cells and is chemoattractant for neutrophils, basophils, and T-cells. IL-8 activates neutrophils in the adipose tissue. Elevated levels are associated with increased risk of coronary artery disease and types I and II diabetes.
• 4.
  IL-10: This interleukin inhibits cytokine production, promotes B cell proliferation and antibody production, and suppresses cellular immunity and mast cell growth. The serum levels of IL-10 are enhanced in obesity primarily from the nonfat cells of the monocytes and it functions as a feedback inhibitor, that is, it prevents the secretion of the inflammatory cytokines. This is the only good cytokine secreted in obesity.
• 5.
  IL-18: Increased levels are associated with increased risks of both diabetes and cardiovascular disease. This cytokine is released more by the nonfat cells of the adipose tissue.

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