ASPIRIN FOR ALZHEIMER’S DISEASE?
When doctors treating alzheimer’s patients took a closer look at who seemed to be succumbing to the disease, they uncovered a tantalizing clue: those who were already taking anti-inflammatory drugs for arthritis or heart disease tended to develop the disorder later than those who weren’t. Perhaps the immune system mistakenly saw the characteristic plaques and tangles that build up in the brains of Alzheimer’s patients as damaged tissue that needed to be cleared out. If so, the ensuing inflammatory reaction was doing more harm than good. Blocking it with anti-inflammatories might limit, or at least delay, any damage to cognitive functions.
The most likely culprits this time around are the glial cells, whose job is to nourish and communicate with the neurons. Researchers have discovered that glial cells can also act a lot like the mast cells of the skin, producing inflammatory cytokines that call additional immune cells into action. “The glial cells are trying to return the brain to a normal state,” explains Linda Van Eldik, a neurobiologist at Northwestern University Feinberg School of Medicine in Chicago. “But for some reason, in neurodegenerative diseases like Alzheimer’s, the process seems to be out of control. You get chronic glial activation, which results in an inflammatory state.”
It appears that some people are more sensitive to plaques and tangles than others. Perhaps they have a genetic predisposition. Or perhaps a long-running bacterial infection, like gum disease, keeps the internal fires burning and tips the balance toward chronic inflammation.
Preliminary research suggests that low-dose aspirin and fish-oil capsules—both of which are known to reduce inflammatory cytokines—seem to reduce a person’s risk of Alzheimer’s disease. Unfortunately, most of these preventive measures need to be started well before any neurological problems develop. “What we’ve learned with dementia is that it’s very hard to improve people who already have it,” says Dr. Ernst Schaefer, a professor of medicine and nutrition at Tuft’s Friedman School of Nutrition in Boston. “But it may be possible to stabilize people and to prevent disease.”
WHEN THE BODY ATTACKS ITSELF
No doctors have more experience treating chronic inflammation than the physicians who specialize in rheumatoid arthritis, multiple sclerosis, lupus and other autoimmune disorders. For decades these diseases have provided the clearest example of a body at war with itself. But the spark that fuels their internal destruction doesn’t come from excess cholesterol deposits or a stubborn bacterial infection. Instead, in a bizarre twist of fate, the body’s supersophisticated, learned immunological defenses mistakenly direct an inflammatory attack against healthy cells in such places as the joints, nerves and connective tissue.
Over the past few years, powerful drugs like Remicade® and Enbrel®, which target specific inflammatory cytokines, have worked wonders against rheumatoid arthritis and other autoimmune disorders. But as often happens in medicine, the drugs have also created some problems. Patients who take Remicade®, for example, are slightly more likely to develop tuberculosis; the same inflammatory cytokines that attacked their joints, it seems, also protected them against TB.
Inflammation may be more of a problem in the earlier stages of autoimmune diseases like multiple sclerosis. So much tissue is eventually destroyed that nerve damage becomes permanent. “Your initial goal is to keep the immune response in check, but then you have to ask how you encourage regrowth of damaged tissue,” says Dr. Stephen Reingold, vice president for research programs at the National Multiple Sclerosis Society. It could take decades to figure that one out.
ASTHMA WITHOUT ALLERGIES?
One of the most intriguing questions in immunology today is why everyone doesn’t suffer from asthma. After all, the air we breathe is full of germs, viruses and other irritants. Since half of the 17 million Americans with asthma are hypersensitive to common substances like cat dander or pollen, it stands to reason that their allergic reactions trigger the chronic inflammation in their bodies. Yet the people who develop asthma as adults—one of the most rapidly growing segments of the population—often don’t have allergies. Doctors still don’t know what’s driving their disease, but the signs of inflammation are every bit as present in their lungs.
Many treatments for asthma are designed to control inflammation, although they still don’t cure the disease. “It may mean that the inflammatory hypothesis is not entirely correct or the drugs that we use to treat inflammation aren’t fully potent,” says Dr. Stephen Wasserman, an allergist at the University of California at San Diego. “There are a lot of gaps to fill in.”
Everywhere they turn, doctors are finding evidence that inflammation plays a larger role in chronic diseases than they thought. But that doesn’t necessarily mean they know what to do about it. “We’re in a quandary right now,” says Dr. Gailen Marshall, an immunologist at the University of Texas Medical School at Houston. “We’re advancing the idea to heighten awareness. But we really can’t recommend specific treatments yet.”
That may soon change. Researchers are looking beyond aspirin and other multipurpose medications to experimental drugs that block inflammation more precisely. Any day now, Genentech is expecting a decision from the FDA on its colon-cancer drug, Avastin™, which targets one of the growth factors released by the body as inflammation gives way to healing. [Avastin™ was approved by the FDA on February 26, 2004.] Millennium Pharmaceu-ticals is testing a different kind of drug, called Velcade, which has already been approved for treating multiple myeloma, against lung cancer and other malignancies. But there is a sense that much more basic research into the nature of inflammation needs to be done before scientists understand how best to limit the damage in chronic diseases.
In the meantime, there are things we all can do to dampen our inflammatory fires. Some of the advice may sound terribly familiar, but we have fresh reasons to follow through. Losing weight induces those fat cells—remember them?—to produce fewer cytokines. So does regular exercise, 30 minutes a day most days of the week. Flossing your teeth combats gum disease, another source of chronic inflammation. Fruits, vegetables and fish are full of substances that disable free radicals.
So if you want to stop inflammation, get off that couch, head to the green market and try not to stub your toe on the way.
—With reporting by Dan Cray/Los Angeles