THE FIRE WITHIN HEALTH EXPERTS TAKING A LONG LOOK AT INFLAMMATION AND ITS LINK TO SERIOUS ILLNESSES.

Byline: Mariko Thompson Staff Writer

The red swelling around a bug bite or a scrape has happened so many times in our lives that we hardly think about this mechanism of the body's defense system - except when it goes awry.

The body uses inflammation to fight injury and infection, from a sprained ankle to the common cold virus. But sometimes, the inflammation process doesn't shut down once the job is done.

Until recently, chronic inflammation was viewed as the domain of specialists in lupus, rheumatoid arthritis and other auto-immune diseases. Now scientists are starting to uncover inflammation's role in a host of other chronic illnesses including such killers as cancer and heart disease.

``This is all relatively new,'' says Dr. Mary Roman, professor of medicine at Weill Cornell Medical Center in New York. ``Things have snowballed since the mid-'90s.''

The role of inflammation has reshaped how cardiologists look at heart disease. Doctors used to talk in terms of clogged pipes, of arteries narrowing with the build-up of plaque. Now they talk about the plaque rupturing and releasing clots as a result of inflammation.

Testing for inflammation levels can even help doctors determine how aggressively they should treat patients at risk for heart disease.

Doctors run a blood test to measure C-reactive protein, a by-product of inflammation. According to the American Heart Association, studies suggest that people with elevated CRP levels have a higher risk of suffering from a heart attack and a lower survival rate.

The test is not recommended for general screenings. Doctors say it's most useful for patients at moderate risk for cardiovascular disease.

``It does have some prognostic value,'' says Dr. Nicholas Di Domenico, an internist at Valley Presbyterian Hospital in Van Nuys. ``The problem is the test is not specific and (CRP levels) could be raised by other diseases. The CRP can be elevated in any kind of infection.''

A recent study by Weill Cornell Medical Center researchers further reinforced the role that inflammation plays in heart disease. Roman, a cardiologist, and Dr. Jane Salmon, a rheumatologist, teamed up to look at atherosclerosis - or hardening of the arteries - in patients with lupus, a chronic inflammatory disease.

Female lupus patients below the age of 55 suffer an unusual number of heart attacks. In the past, those heart attacks had been attributed to the use of an immunosuppressant medication that can cause hypertension and diabetes, both heart disease risk factors. The Weill Cornell study compared female lupus patients to a control group with similar cardiovascular disease risk factors. Researchers found that having lupus increased the likelihood of atherosclerosis by 140 percent. In women under 40, the risk skyrocketed by 480 percent.

``Inflammation plays a role in the population as a whole in terms of causing heart attacks,'' Roman says. ``But when you've got lupus or rheumatoid arthritis, it's like having a concentrated dose. That's what makes it happen so much earlier.''

A Vanderbilt University study released at the same time had similar findings. Roman said the results could lead to better treatment strategies. Researchers can investigate an anti-inflammatory medication with fewer side effects for lupus patients. Or they can identify a marker for atherosclerosis and create a targeted medication, she says.

That next step is where it can get tricky. Sometimes, researchers are able to establish a direct link between inflammation and treatment. In the area of colon cancer, taking a daily baby aspirin - an anti-inflammatory - has been found to reduce the risk of advanced colon lesions by up to 40 percent.

In other areas, the link remains elusive. In studies of mice, scientists found too much COX-2 protein - which is involved in the inflammation process - mimicked memory problems in Alzheimer's disease. But so far, studies of COX-2 inhibitors on Alzheimer's patients haven't yielded dramatic improvements, says Dr. Daniel Arkfeld, assistant professor of clinical medicine and rheumatology at the USC Keck School of Medicine.

What causes inflammation to spin out of control isn't well understood. And shutting off the flow is more complicated than turning a faucet. Molecules called cytokines are believed to trigger much of the inflammation in the body. But there are numerous types of cytokines. Pinpointing which one in the chain initiated the process is a challenge, Arkfeld says.

In the area of rheumatoid arthritis, researchers have been able to identify some key cytokines and develop blocking medications, Arkfeld says.

``With these cytokine blockers, we're keeping people with debilitating illnesses functional,'' he says. ``These drugs are fairly phenomenal.''

So what does all this talk about inflammation mean to the average person? From a preventive standpoint, the use of anti-inflammatories is limited by side effects. Long-term use of even ibuprofen or aspirin, basic over-the-counter medications, can lead to gastrointestinal bleeding.

``It's a delicate balance,'' Arkfeld says. ``You can flip people into a worse condition.''

That's why Arkfeld doubts that anti-inflammatory pills will have a place alongside daily multivitamins. The path that holds more promise is learning how to reset a person's genes. In that futuristic scenario, a patient with a cancer gene has the gene removed, rather than trying to control inflammation, he says.

``Once we can splice them out, that's where the greatest potential benefit will be.''

Mariko Thompson, [phone]

mariko.thompson(at)dailynews.com

CAPTION(S):

3 photos

Photo:

(1 -- cover -- color) HOT DEBATE

Doctors ponder role of inflammation in chronic disease

(2) no caption (body with chronic inflammation)

Jon Gerung/Staff Artist

(3) no caption (body with chronic inflammation)

Michael Owen Baker/Staff Photographer