(2 of 5)
— 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 Pharmaceuticals 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.
Is Your Heart on Fire?
Not long ago, most doctors thought of heart attacks as primarily a plumbing problem. Over the years, fatty deposits would slowly build up on the insides of major coronary arteries until they grew so big that they cut off the supply of blood to a vital part of the heart. A complex molecule called LDL, the so-called bad cholesterol, provided the raw material for these deposits. Clearly anyone with high LDL levels was at greater risk of developing heart disease.