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Aging and Inflammation

By: Peter T. Pugliese, MD
Posted: November 24, 2009, from the December 2009 issue of Skin Inc. magazine.

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The T helper 1 (TH1) cells produce a number of cytokines, including interferon-gamma (IFN-γ), reactive oxygen species (ROS), lipid species and other proinflammatory cytokines. The T helper 2 (TH2) cells stimulate long-term immunity through the production of a number of cytokines that induce B cell maturation resulting in antibody-producing special cells called plasma cells. TH2 cells can also call out more mast cells and contribute to chronic inflammation.

Chronic inflammation and aging

A key concept to understanding chronic inflammation is that signals from both the innate and adaptive immune systems combine, interact and affect two types of body cells: the epithelial cells and one or more mesenchymal cells of whatever organ is under attack. It is interesting that regardless of the disease that may result, ranging from arthritis to heart disease, the same inflammatory process is at work from the recruitment of leukocytes, extracellular matrix remodeling, proliferation of cells or cellular death, and even the building of new blood vessels, called angiogenesis. Both types of helper T cells are present in large numbers, which can create widespread tissue damage. Why? Why would the immune system attack its own body cells?

Normally the immune system would not attack a component such as blood vessels, and, in fact, the endothelial cells lining the interiors of blood vessels would resist any attack by white blood cells. After all, trillions of white blood cells are racing through blood vessels every minute of every day. However, if anything disrupts the integrity of these endothelial cells, such as bacteria, abnormal lipoprotein or even an active cytokine with a mind for destruction, the endothelial cell will respond by secreting a substance called vascular cell adhesion molecule-1 (VCAM-1).

Now the trouble begins. This type I membrane protein mediates leukocyte-endothelial cell adhesion and signal transduction, and has been implicated in the development of artherosclerosis and rheumatoid arthritis. VCAM-1 promotes the adhesion of white blood cells such as lymphocytes, monocytes, eosinophils and basophils.

Cytokines. Two important subjects in immunology are cytokines and transcription factors. Cytokines are chemical compounds that get cells moving. They come in three flavors—proteins, peptides and glycoproteins—and they are powerful, actually 1,000 times more powerful than regular hormones. For example, while hormones are effective at levels of nanomoles, cytokines are effective at picomoles. A nanomole is one billionth of a molecular weight, while a picomole is one trillionth of a molecular weight. A mole is the weight of one molecule of a substance in grams.