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Inflammation as enemy

An immune reaction may contribute to diabetes, heart disease and Alzheimer's. Doctors are shifting focus to the common thread.

April 17, 2006|Judy Foreman | Special to The Times

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

There's no grand proof of this "theory of everything." But doctors say the evidence is compelling enough that we should act as if it were true -- which means eating an "anti-inflammatory diet," getting lots of physical activity and losing the fat that pumps out the chemicals that drive inflammation.

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

But when the inflammation process fails to shut off after an infection or injury is over, trouble sets in. Many doctors now think persistent, low-level inflammation may pave the way for the chronic diseases of later life.

For The Record
Los Angeles Times Tuesday April 18, 2006 Home Edition Main News Part A Page 2 National Desk 0 inches; 24 words Type of Material: Correction
Inflammation: In Monday's Health section, an article on chronic inflammation referred to cytokines as inflammatory cells. Cytokines are proteins released by some immune cells.
For The Record
Los Angeles Times Monday April 24, 2006 Home Edition Health Part F Page 6 Features Desk 0 inches; 27 words Type of Material: Correction
Inflammation -- An article on chronic inflammation in the April 17 Health section referred to cytokines as inflammatory cells. Cytokines are proteins released by some immune cells.

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 Brigham and Women's Hospital in Boston. "Now, the lifespan 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 gets embedded inside artery walls as well, where the immune system "sees" it as an invader to be attacked. The ongoing inflammation in arteries, essentially a revved up immune response, can eventually damage arteries and cause "vulnerable" plaque to burst. It is because inflammation is now 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.

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 occurs in 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 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," said Libby. "Now we know that fat cells are little hotbeds of inflammation -- excess fat in the belly is a great source of inflammation."

Auto-immune 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 Northwestern University's 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, and 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 UCLA 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, said Dr. Robert Tepper, president of research and development for Millennium Pharmaceuticals in Cambridge, Mass. Chemokines, the same protein-signaling molecules 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 spreading and the inflammatory response.

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