Chronic inflammation may be connected to medical maladies


April 07, 2006|By JUDY FOREMAN

The idea is as simple as it is radical: Chronic inflammation, spurred by an immune system run amok, appears to play a role in medical evils from arthritis to Alzheimer's, from diabetes to heart disease.

There's no grand proof of this "theory of everything." But doctors say it's compelling enough that we should act as if it were true -- which means eating an "anti-inflammatory diet," doing lots of physical activity, and losing the dangerous, internal belly fat that pumps out the chemicals that drive inflammation (more on this nasty chemistry later).

Inflammation, of course, is not all bad. In fact, because it's part of the typical immune response, it's essential for battling germs and healing wounds. The familiar redness, heat, swelling and pain that come from, say, a hangnail or a splinter are signs of inflammation at work.

It's when the inflammation process fails to shut off after an infection or injury is over that trouble sets in. Persistent, low-level inflammation may set the stage for the chronic diseases of later life, many doctors now believe.

Over the evolutionary eons, "we developed these important host defenses to let us get to reproductive age," said Dr. Peter Libby, chief of cardiovascular medicine at Boston's Brigham and Women's Hospital. "Now, the life span has almost doubled, and these same [immune responses] contribute to diseases in the end."

Chronic inflammation is so similar in different diseases, Libby said, that when he lectures, he uses many of the same slides, whether he's talking about diseases of the heart, kidneys, joints, lung or other tissues.

Only a few years ago, heart attacks were explained as a plumbing problem -- blood vessels that became clogged with atherosclerotic plaque as "bad" (LDL) cholesterol was deposited on vessel walls.

Now doctors know that this bad cholesterol becomes embedded inside artery walls as well, where the immune system "sees" it as an invader to be attacked. The inflammation in arteries, essentially a revved-up immune response, can damage arteries and cause "vulnerable" plaque to burst.

It is because inflammation is seen as such a hallmark of heart disease that many doctors use a test for inflammation called CRP to help assess a person's cardiac risk.

Diabetes connection

It's long been known that type 1 diabetes is linked to inflammation -- the body's immune system attacks the cells that make insulin. New research is suggesting that type 2 diabetes, the kind that generally sets in during adulthood, often begins with insulin resistance, in which cells stop responding properly to insulin. Doctors now know that during chronic inflammation, one of the chemicals released is TNF, or tumor necrosis factor, which makes cells more resistant to insulin.

"No one would have thought these things were related," but they are, said Dr. Walter Willett, chairman of the department of nutrition at the Harvard School of Public Health.

The TNF connection also helps explain why obesity, particularly abdominal obesity, leads to diabetes. "Fat cells used to be thought of as storage depots for energy, as metabolically inactive," Libby said. "Now we know that fat cells are little hotbeds of inflammation -- excess fat in the belly is a great source of inflammation."

Autoimmune diseases such as rheumatoid arthritis are also believed to be linked to inflammation. In arthritis, for instance, inflammatory cells called cytokines lead to the production of enzymes that break down cartilage in joints.

Inflammation also plays some role in Alzheimer's disease, said Linda Van Eldik, a neurobiologist at the Northwestern University Feinberg School of Medicine.

Whenever the brain is injured or infected, cells in the brain called glia pump out cytokines. Normally, this response shuts down when the injury or infection is over.

"But in chronic neurodegenerative diseases like Alzheimer's, these glial cells are activated too high or too long or both," Van Eldik said. The plaques and tangles in patients' brains attract the attention of glial cells, making them pump out even more cytokines to try to repair this damage, creating chronic inflammation.

Even cancer may have some inflammatory triggers, though the links are less well worked out, said Dr. David Heber, director of the University of California, Los Angeles Center for Human Nutrition. Among its other tricks, inflammation promotes the release of free radicals, dangerous forms of oxygen that can damage DNA. At chronic, low doses, Heber said, "free radicals can stimulate tumors to grow."

There are other chemical overlaps between inflammation and cancer too, said Dr. Robert Tepper, president of research and development for Millennium Pharmaceuticals in Cambridge, Mass. The same protein-signaling molecules called chemokines that tell white blood cells when to flock to an injury or infection also tell cancer cells when and where to spread, suggesting a link between cancer spread and the inflammatory response.

Cut your risk

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