Immune Systems Increasingly On Attack

[Guest guest]

By Rob Stein

Washington Post Staff Writer

Tuesday, March 4, 2008; Page A01

First, asthma cases shot up, along with hay fever and other common allergic

reactions, such as eczema. Then, pediatricians started seeing more children

with food allergies. Now, experts are increasingly convinced that a

suspected jump in lupus, multiple sclerosis and other afflictions caused by

misfiring immune systems is real.

Though the data are stronger for some diseases than others, and part of the

increase may reflect better diagnoses, experts estimate that many allergies

and immune-system diseases have doubled, tripled or even quadrupled in the

last few decades, depending on the ailment and country. Some studies now

indicate that more than half of the U.S. population has at least one

allergy.

The cause remains the focus of intense debate and study, but some

researchers suspect the concurrent trends all may have a common explanation

rooted in aspects of modern living -- including the " hygiene hypothesis "

that blames growing up in increasingly sterile homes, changes in diet, air

pollution, and possibly even obesity and increasingly sedentary lifestyles.

" We have dramatically changed our lives in the last 50 years, " said

ez, who studies allergies at the University of Arizona. " We are

exposed to more products. We have people with different backgrounds being

exposed to different environments. We have made our lives more antiseptic,

especially early in life. Our immune systems may grow differently as a

result. And we may be paying a price for that. "

Along with a flurry of research to confirm and explain the trends,

scientists have also begun testing possible remedies. Some are feeding

high-risk children gradually larger amounts of allergy-inducing foods,

hoping to train the immune system not to overreact. Others are testing

benign bacteria or parts of bacteria. Still others have patients with MS,

colitis and related ailments swallow harmless parasitic worms to try to calm

their bodies' misdirected defenses.

" If you look at the incidence of these diseases, a lot of them began to

emerge and become much more common after parasitic worm diseases were

eliminated from our environment, " said Summers of the University of

Iowa, who is experimenting with whipworms. " We believe they have a profound

symbiotic effect on developing and maintaining the immune system. "

Although hay fever, eczema, asthma and food allergies seem quite different,

they are all " allergic diseases " because they are caused by the immune

system responding to substances that are ordinarily benign, such as pollen

or peanuts. Autoimmune diseases also result from the body's defense

mechanisms malfunctioning. But in these diseases, which include lupus, MS,

Type 1 diabetes and inflammatory bowel disease, the immune system attacks

parts of the body such as nerves, the pancreas or digestive tract.

" Overall, there is very little doubt that we have seen significant

increases, " said Syed Hasan Arshad of the Hide Asthma and Allergy

Centre in England, who focuses on food allergies. " You can call it an

epidemic. We're talking about millions of people and huge implications, both

for health costs and quality of life. People miss work. Severe asthma can

kill. Peanut allergies can kill. It does have huge implications all around.

If it keeps increasing, where will it end? "

One reason that many researchers suspect something about modern living is to

blame is that the increases show up largely in highly developed countries in

Europe, North America and elsewhere, and have only started to rise in other

countries as they have become more developed.

" It's striking, " said Cookson of the Imperial College in London.

The leading theory to explain the phenomenon holds that as modern medicine

beats back bacterial, viral and parasitic diseases that have long plagued

humanity, immune systems may fail to learn how to differentiate between real

threats and benign invaders, such as ragweed pollen or food. Or perhaps

because they are not busy fighting real threats, they overreact or even turn

on the body's own tissues.

" Our immune systems are much less busy, " said Jean-Francois Bach of the

French Academy of Sciences, " and so have much more strong responses to much

weaker stimuli, triggering allergies and autoimmune diseases. "

Several lines of evidence support the theory. Children raised with pets or

older siblings are less likely to develop allergies, possibly because they

are exposed to more microbes. But perhaps the strongest evidence comes from

studies comparing thousands of people who grew up on farms in Europe to

those who lived in less rural settings. Those reared on farms were one-tenth

as likely to develop diseases such as asthma and hay fever.

" The data are very strong, " said von Mutius of the Ludwig-Maximilians

University in Munich. " If kids have all sorts of exposures on the farm by

being in the stables a lot, close to the animals and the grasses, and

drinking cow's milk from their own farm, that seems to confer protection. "

The theory has also gained support from a variety of animal studies. One,

for example, found that rats bred in a sterile laboratory had far more

sensitive immune systems than those reared in the wild, where they were

exposed to infections, microorganisms and parasites.

" It's sort of a smoking gun of the hygiene hypothesis, " said

of Duke University.

Researchers believe the lack of exposure to potential threats early in life

leaves the immune system with fewer command-and-control cells known as

regulatory T cells, making the system more likely to overreact or run wild.

" If you live in a very clean society, you're not going to have a lot of

regulatory T cells, " said.

While the evidence for the hygiene theory is accumulating, many say it

remains far from proven.

" That theory is so full of holes that it's clearly not the whole story, "

said Wood of the s Hopkins School of Medicine.

It does not explain, for example, the rise in asthma, since that disease

occurs much more commonly in poor, inner-city areas where children are

exposed to more cockroaches and rodents that may trigger it, Wood and others

said.

Several alternative theories have been presented. Some researchers blame

exposure to fine particles in air pollution, which may give the immune

system more of a hair trigger, especially in genetically predisposed

individuals. Others say obesity and a sedentary lifestyle may play a role.

Still others wonder whether eating more processed food or foods processed in

different ways, or changes in the balance of certain vitamins that can

affect the immune system, such as vitamins C and E and fish oil, are a

factor.

" Cleaning up the food we eat has actually changed what we're eating, " said

Platts-Mills of the University of Virginia.

But many researchers believe the hygiene hypothesis is the strongest, and

that the reason one person develops asthma instead of hay fever or eczema or

lupus or MS is because of a genetic predisposition.

" We believe it's about half and half, " Cookson said. " You need environmental

factors and you need genetic susceptibility as well. "

Some researchers have begun to try to identify specific genes that may be

involved, as well as specific components of bacteria or other pathogens that

might be used to train immune systems to respond appropriately.

" If we could mimic what is happening in these farm environments, we could

protect children and prevent asthma, allergies and other diseases, " von

Mutius said.

Some researchers are trying to help people who are at risk for allergies or

already ill with autoimmune diseases.

With new research suggesting that food allergies may be occurring earlier in

life and lasting longer, several small studies have been done or are

underway in which children at risk for milk, egg and peanut allergies are

given increasing amounts of those foods, beginning with tiny doses, to try

to train the immune system.

" I'm very encouraged, " said Wesley Burks, a professor of pediatrics at Duke

who has done some of the studies. " I'm hopeful that in five years, there may

be some type of therapy from this. "

Another promising line of research involves giving patients microscopic

parasitic worms to try to tamp down the immune system.

" We've seen rather dramatic improvements in patients' conditions, " said

Summers of the University of Iowa, who has treated more than 100 people with

Crohn's disease or ulcerative colitis by giving them parasitic worms that

infect pigs but are harmless to humans. " We're not claiming that this is a

cure, but we saw a very dramatic improvement. Some patients went into

complete remission. "

Doctors in Argentina reported last year that MS patients who had intestinal

parasites fared better than those who did not, and researchers at the

University of Wisconsin are planning to launch another study as early as

next month testing pig worms in 20 patients with the disease.

" We hope to show whether this treatment has promise and is worth exploring

further in a larger study, " said O. Fleming, a professor of neurology

who is leading the effort.