What does a stubbed toe or a splinter in a finger have to do with your risk of developing Alzheimer’s disease, suffering a heart attack or succumbing to colon cancer? More than you might think. As scientists delve deeper into the fundamental causes of those and other illnesses, they are starting to see links to an age-old immunological defense mechanism called inflammation—the same biological process that turns the tissue around a splinter red and causes swelling in an injured toe. If they are right—and the evidence is starting to look pretty good—it could radically change doctors’ concept of what makes us sick. It could also prove a bonanza to pharmaceutical companies looking for new ways to keep us well.
Most of the time, inflammation is a lifesaver that enables our bodies to fend off various disease-causing bacteria, viruses and parasites. (Yes, even in the industrialized world, we are constantly bombarded by pathogens.) The instant any of these potentially deadly microbes slips into the body, inflammation marshals a defensive attack that lays waste to both invader and any tissue it may have infected. Then just as quickly, the process subsides and healing begins.
Every once in a while, however, the whole feverish production doesn’t shut down on cue. Sometimes the problem is a genetic predisposition; other times something like smoking or high blood pressure keeps the process going. In any event, inflammation becomes chronic rather than transitory. When that occurs, the body turns on itself—like an ornery child who can’t resist picking a scab—with aftereffects that seem to underlie a wide variety of diseases.
Suddenly, inflammation has become one of the hottest areas of medical research.
Hardly a week goes by without the publication of yet another study uncovering a new way that chronic inflammation does harm to the body. It destabilizes cholesterol deposits in the coronary arteries, leading to heart attacks and potentially even strokes. It chews up nerve cells in the brains of Alzheimer’s victims. It may even foster the proliferation of abnormal cells and facilitate their transformation into cancer. In other words, chronic inflammation may be the engine that drives many of the most feared illnesses of middle and old age.
This concept is so intriguing because it suggests a new and possibly much simpler way of warding off disease. Instead of different treatments for, say, heart disease, Alzheimer’s and colon cancer, there might be a single, inflammation-reducing remedy that would prevent all three.
Chronic inflammation also fascinates scientists because it indicates that our bodies may have, from an evolutionary perspective, become victims of their own success. “We evolved as a species because of our ability to fight off microbial invaders,” says Dr. Peter Libby, chief of cardiovascular medicine at Brigham and Women’s Hospital in Boston. “The strategies our bodies used for survival were important in a time when we didn’t have processing plants to purify our water, when we didn’t have sewers to protect us.”
But now that we are living longer, those same inflammatory strategies are more likely to slip beyond our control. Making matters worse, it appears that many of the attributes of a Western lifestyle—such as a diet high in sugars and saturated fats, accompanied by little or no exercise—also make it easier for the body to become inflamed.
At least that’s the theory. For now, most of the evidence is circumstantial. (A few researchers think chronic inflammation can in some cases be good for you.) But that hasn’t stopped doctors from testing the anti-inflammatory drugs that are already on pharmacy shelves to see if they have any broader benefits. What they’ve found is encouraging:
Heart Disease: Cholesterol molecules slip into the lining of coronary arter ies and are engulfed by cells called macrophages. Eventually, a plaque forms. The stronger the inflammatory reaction, the more likely the plaque will burst, causing a heart attack or stroke
- In 2000 researchers concluded that patients who take Celebrex®, a prescription drug from Pfizer that was originally designed to treat inflammation in arthritis, are less likely to develop intestinal polyps—abnormal growths that can become cancerous. Now there are dozens of clinical trials of Celebrex®, testing, among other things, whether the medication can also prevent breast cancer, delay memory loss or slow the progression of the devastating neurodegenerative disorder known as Lou Gehrig’s disease.
- As cardiologists gain more experience prescribing cholesterol-lowering statins, they are discovering that the drugs are more effective at preventing heart attacks than anyone expected. It turns out that statins don’t just lower cholesterol levels; they also reduce inflammation. Now statins are being tested for their anti-inflammatory effects on Alzheimer’s disease and sickle-cell anemia.
- DeCode Genetics, an Icelandic biotech firm, announced last week that it is launching a pilot study to test whether an anti-inflammatory drug that was under development for use in treating asthma might work to prevent heart attacks.
- Of course the granddaddy of all anti-inflammatories is aspirin, and millions of Americans already take it to prevent heart attacks. But evidence is growing that it may also fight colon cancer and even Alzheimer’s by reducing inflammation in the digestive tract and the brain.
This new view of inflammation is changing the way some scientists do medical research. “Virtually our entire R.-and-D. effort is [now] focused on inflammation and cancer,” says Dr. Robert Tepper, president of research and development at Millennium Pharmaceu-ticals in Cambridge, Mass. In medical schools across the U.S., cardiologists, rheumatologists, oncologists, allergists and neurologists are all suddenly talking to one another—and they’re discovering that they’re looking at the same thing. The speed with which researchers are jumping on the inflammation bandwagon is breathtaking. Just a few years ago, “nobody was interested in this stuff,” says Dr. Paul Ridker, a cardiologist at Brigham and Women’s Hospital who has done some of the groundbreaking work in the area. “Now the whole field of inflammation research is about to explode.”
To understand better what all the excitement is about, it helps to know a little about the basic immunological response, a cascade of events triggered whenever the body is subjected to trauma or injury. As soon as that splinter slices into your finger, for example, specialized sentinel cells prestationed throughout the body alert the immune system to the presence of any bacteria that might have come along for the ride. Some of those cells, called mast cells, release a chemical called histamine that makes nearby capillaries leaky. This allows small amounts of plasma to pour out, slowing down invading bacteria, and prepares the way for other faraway immune defenders to easily enter the fray. Meanwhile, another group of sentinels, called macrophages, begin an immediate counterattack and release more chemicals, called cytokines, which signal for reinforcements. Soon, wave after wave of immune cells flood the site, destroying pathogens and damaged tissue alike—there’s no carrying the wounded off the battlefield in this war. (No wonder the ancient Romans likened inflammation to being on fire.)
Doctors call this generalized response to practically any kind of attack innate immunity. Even the bodies of animals as primitive as starfish defend themselves this way. But higher organisms have also developed a more precision-guided defense system that helps direct and intensify the innate response and creates specialized antibodies, custom-made to target specific kinds of bacteria or viruses. This so-called learned immunity is what enables drug companies to develop vaccines against diseases like smallpox and the flu. Working in tandem, the innate and learned immunological defenses fight pitched battles until all the invading germs are annihilated. In a final flurry of activity, a last wave of cytokines is released, the inflammatory process recedes, and healing begins.
Problems begin when, for one reason or another, the inflammatory process persists and becomes chronic; the final effects are varied and depend a lot on where in the body the runaway reaction takes hold. Among the first to recognize the broader implications were heart doctors who noticed that inflammation seems to play a key role in cardiovascular disease.