Scott LaFee, Copley News Service
INFLAMMATION ISN'T pretty. And it often hurts. But the tell-tale swelling and ache, the redness and heat are signs that our bodies are fighting back against microbial invaders that might otherwise harm or kill us. Inflammation is our first line of defence and sometimes, it now seems, our worst enemy.
In multiple sclerosis, lupus and rheumatoid arthritis, the body turns upon itself with often catastrophic results. But the danger is not limited to these classic inflammatory diseases. Increasingly, scientists are linking inflammation to an expanding list of disparate and sometimes surprising diseases, from Alzheimer's, autism and asthma to cirrhosis, cardiovascular disease and cancer.
"We're converging toward what I believe may eventually be a unifying hypothesis of human disease," said Michael Karin, a molecular biologist and professor of pharmacology at University of California San Diego. "I think we will find that inflammation and infection will account for 90 per cent of human misery."
The evidence is compelling. For example, the Women's Health Study, a landmark research programme involving almost 28,000 women, has found that women with the highest measures of inflammation in their blood face a seven-fold increased risk of heart attack or stroke. Sufferers of inflammatory bowel disease have a five- to seven-fold higher incidence of developing colon cancer. And studies have shown that people who take anti-inflammatory drugs seem to get Alzheimer's disease later in life than those who do not.
"Inflammation may be driving a lot of what we're seeing, in a lot of different diseases. It may be that the things that cause these diseases are related to inflammation," said Dr. Barrett Rollins, chief science officer at the Dana-Farber Cancer Institute in Boston.
"But that being said, there are still a lot of things we need to learn."
BASIC BIOLOGY
The basics, though, are pretty well-known. Inflammation is the body's biggest weapon, the biological equivalent of shock and awe. It is meant to overwhelm and destroy an enemy regardless of collateral damage in an effort to secure quick and total victory. The fundamental process is the same whether you're sneezed upon by someone with a cold, inhale a snoutful of allergenic pollen or cut your finger.
For illustration purposes, let's say the last happens, triggering a cascade of events known collectively as innate immunity.
Sentries called mast cells in the injured finger (they're stationed everywhere) detect the presence of pathogens and sound the alarm, secreting proteins called cytokines to summon help and histamines to make nearby capillaries suddenly porous. The leaky blood vessels flood the wounded area with plasma, producing swelling and discomfort, but also isolating pathogens from the rest of the body and slowing their spread.
Soon, the body's immunological warriors, a class of white blood cells called phagocytes, arrive. They are meat-eaters. Their job is to engulf and digest foreign material, including dead and dying cells.
As the phagocytes work, they secrete more cytokines, summoning more reinforcements and provoking greater and sharper symptoms of inflammation. Their fight will rage on until there is nothing left to kill or eat.
CHRONIC INFLAMMATION
Under normal circumstances, said Geert Schmid-Schoenbein, a University of California San Diego professor of bioengineering, "once the infection is cleared up, inflammation goes away." The phagocytes die. The wound heals. Tissues return to normal.
Only sometimes the process doesn't stop. Sometimes inflammation smolders like a fire within. It becomes chronic, though its consequences might not be immediately noticed or felt. Why this happens is not fully understood, but the tally of known or suspected causes of chronic inflammation is long and growing.
Some people appear to be genetically predisposed to chronic inflammation. Obesity is a huge factor. Fat cells, researchers have discovered, produce and spew their own pro-inflammatory cytokines. The fatter you are, say scientists, the bigger the threat of chronic inflammation.
Bacteria and viruses provoke an inflammatory response, and when they linger in conditions like gum disease and stomach ulcers, they foster a chronic inflamed state, even though the sufferer may initially feel no ill effect.
EXTERNAL STIMULI
Numerous environmental and external stimuli have been linked to chronic inflammation. Among them: asbestos, smoking, coffee, alcohol, birth control pills, some medical treatments such as hormone replacement therapy, even prolonged or recurrent bouts of anger, hostility and depression.
"Every time we look for signs of inflammation, we find them," said Schmid-Schoenbein. "Even in apparently young, healthy, asymptomatic college students who consume tobacco products."
It has only been in the last decade - and most keenly in just the last few years that researchers have begun to identify chemical biomarkers that signal inflammation even when symptoms are not present or obvious.
These biomarkers tend to be the working elements and products of inflammation: the various proteins, chemicals and cells that, in a normal, healthy state, are present only in modest amounts, if at all.
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