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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:
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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
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- 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.
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