To head off allergies, expose your kids to pets and dirt

To head off allergies, expose your kids to pets and dirt early. Really.

By Steve Sternberg, USA TODAY Mon Mar 20, 6:38 AM ET

Here's the conventional wisdom: Pets promote allergy, kids shouldn't eat peanuts until they're at least 3, and intestinal worms are nothing more than an icky reminder of life before flush toilets.


Here's the new wisdom: Early exposure to pets, peanuts and intestinal worms might actually be good for you, because they program the developing immune system to know the difference between real threats, such as germs, and Aunt Millie's cat. (Graphic: Short-circuiting a cat allergy)

Evidence to support this view has been mounting for more than a decade. But now, for the first time, researchers are beginning to test remedies based on these theories in patients. Other doctors are trying to make use of novel approaches to retrain the immune system once it's too late and allergies set in.

"What we've learned is that it may, in fact, be important to be exposed early on to a sufficient quantity of allergy-causing substances to train the immune system that they are not a threat," says Andy Saxon of the University of California-Los Angeles. "And, in people who already have allergies, we see for the first time where the problems lie, and we have new opportunities to tweak the system."

Scientists base this radical new thinking about human allergies on a deeper understanding of how the immune system works. They have begun to exploit fresh insights to attack allergies and other immune diseases in unexpected ways. No longer content just to treat allergy symptoms, they hope to outwit the immune system and stop allergic responses before they start.

"When you're born, Day Zero, your immune system is like a new computer. It's not programmed. You have to add software," says Joel Weinstock of Tufts New England Medical Center. "Between the ages of zero and 12, you're learning to read, you're learning to write, and your immune system is learning to react to things. Part of that is learning to limit reactivity."

If the new approaches work, millions might benefit. More than 50 million people have allergic diseases, which are the sixth-leading cause of chronic illness in the USA, according to the National Institute of Allergy and Infectious Diseases (NIAID), costing the health system $18 billion a year.

Asthma alone accounts for 500,000 hospitalizations a year, including 2 million admissions to the emergency room, says a study in the May 2005 Journal of Allergy and Clinical Immunology. Since 1980, adult asthma cases have risen by 75% and childhood asthma by 160%, the Centers for Disease Control and Prevention reports. (Related: Asthmatic kids under a cloud)

To test whether high-dose exposure breeds tolerance, researchers led by Gideon Lack at Imperial College in London are preparing to launch a counterintuitive - and some would say risky - seven-year, U.S.-financed study that will expose infants to peanuts. It's based on research showing that children who eat peanuts at an early age are less likely to develop peanut allergies.

The study is risky because children with unrecognized peanut allergies might suffer anaphylactic shock, a deadly drop in blood pressure often combined with asthma, if they're exposed to peanuts.

A second team of researchers, led by Patrick Holt of the University of Western Australia in Perth, will conduct a similar study in which children who are already allergic to other substances will be exposed to airborne allergens such as ragweed to see whether it will block the development of other allergies.

Other studies suggest that short-lived infections with a benign parasite might relieve allergies and possibly autoimmune illnesses such as Crohn's disease and Type I diabetes by restoring the immune system's natural balance. Major human trials in the USA and Europe are set to begin this year.

Although trying to link allergies to autoimmune diseases such as Crohn's might seem like a stretch, scientists say both types of ailments result from an immune system run amok. In allergies, the immune system goes on alert when ragweed or some other allergy-causing protein wafts through the air, settles on the skin or tickles the tongue. In autoimmune diseases, the immune system can no longer distinguish between the self and foreign proteins. Mistaking the self for those proteins, the immune system attacks the bowel in Crohn's disease or insulin-producing cells in Type 1 diabetes.

Early intervention

If educating the immune system is tough, re-educating it after allergies set in appears to be tougher. Allergy shots work, but they're costly and often must be continued for years, and the protection fades over time. Higher-tech approaches rely heavily on 21st-century molecular medicine to engineer proteins that block allergies.

One strategy, pioneered by researchers at Dynavax Technologies in Berkeley, Calif., involves disguising a key ragweed protein with DNA from a bacterium. The goal: to create a new short course of allergy shots that tricks the immune system into permanently thinking that ragweed is a bacterium, so it will attack it like a germ and not mount an allergic response. The approach has appeared to work in early trials at Johns Hopkins University.

A second strategy, now being developed by Saxon and his colleagues at UCLA and licensed to the biotech firm Biogen Idec, involves fusing a cat allergen with a snippet of a powerful antibody called IgG. This IgG snippet turns off cells that make histamine, the chemical responsible for scratchy throats, watery eyes, runny noses and asthma. Researchers hope the combo will lock histamine-producing cells in the off position, and, in time, retrain the immune system to accept that Aunt Millie's cat is harmless.

Hypothetically speaking

The new approach to allergy prevention and treatment arises from a paradox. Known as the hygiene hypothesis, it suggests that growing up in cities and suburbs, away from fields and farm animals, leaves people more susceptible to a host of immune disorders, including allergies and asthma.

Weinstock says the divide between developed and undeveloped countries is still evident today. "Hay fever is the most common allergy in the developed world," he says. "Yet, there are some countries in the world where doctors don't know what hay fever is."

What about urban life is triggering a rash of allergies and autoimmune diseases? It's a good question, and not an easy one to answer. The immune system isn't palpable as are the heart and lungs; you can't listen to it or feel its pulse. Yet the immune system is our most sensitive link to the environment, on alert for threats of all kinds, most of the time running in the background like computer anti-virus software.

To accelerate the research, the
National Institutes of Health and the Juvenile Diabetes Research Foundation in 1999 set up a seven-year, $144 million international consortium called the Immune Tolerance Network, says Marshall Plaut of NIAID. Already, research is turning up surprising results.

Dennis Ownby of the Medical College of Georgia followed 474 infants in the Detroit area from birth to age 7, hoping to identify clues about why some would pick up allergies and others would not. Ownby, then at Henry Ford Hospital, says he was unprepared for what he found.

Ownby's team compared 184 children who were exposed to two or more dogs or cats in their first year of life with 220 who didn't have pets. To their surprise, the scientists found that children raised with pets were 45% less likely to test positive for allergies than other kids. The study appeared in the Aug. 28, 2002
Journal of the American Medical Association.

"We've been taught for at least a couple of decades that early exposure to an allergen increases the risk of becoming allergic later in life," Ownby says. "So when we first examined our data, we were very afraid that something had gone wrong. It's the opposite of what we would have predicted."

The challenge now, Ownby says, is to figure out what's happening. One possible explanation is that dogs and cats shed a substance called endotoxin, from bacteria. A study by Andy Liu of National Jewish Medical and Research Center in Denver reported in 2000 that infants with the most endotoxin exposure were the least likely to have allergies, indicating that what researchers call the Pigpen Effect, the invisible cloud of dust and dirt surrounding us all, might not be a bad thing.

Or consider the peanut paradox. In the past 10 years, peanut allergies have doubled in the USA, United Kingdom and other countries that advise against exposing unborn children to peanuts (through their mothers' diet) and during infancy, Imperial College's Lack says. He believes children become allergic to peanuts not by eating them but by coming into contact with peanut oil in their mothers' skin lotions, according to a study published in the March 2003
New England Journal of Medicine. Studies of rodents suggest eating peanuts conditions the immune system to tolerate them.

Infants in regions of Africa and Asia who are exposed to peanuts rarely develop the allergy, Lack says, in contrast to countries such as the USA and UK, where the prevalence of peanut allergies might be more than 10 times higher.

To test whether eating peanut products can protect children from peanut allergies, Lack plans to launch a dramatic seven-year study in which parents will regularly feed high doses of peanuts to about 200 children who have egg allergies or eczema, conditions that put them at high risk of developing other allergies. Parents of another 200 children will follow the government's advice and try to completely avoid peanuts.

One key message, Lack says, is don't try this at home, without the safeguards of a carefully controlled trial. "Feeding babies peanuts can be extremely dangerous," he says.

As high-risk as the trial is, it might be extremely rewarding, doctors say. Each year in the USA, about 15,000 people suffer severe allergic reactions from eating peanuts, and about 100 die.

"It's the first large-scale trial of what we consider a very dangerous allergic food," Ownby says.

To the squeamish, it might not matter that intestinal worms are less risky than foods that promote allergy. But some doctors say worms might do something that allergy-causing substances won't do - broadly reset the immune system so that it no longer reacts to allergy-causing substances or attacks the body's tissues, as it does in Crohn's disease and Type I diabetes. "This is an exciting new area with potential for opening new therapeutic avenues for diseases that are hard to control and treat," says Weinstock of Tufts New England Medical Center.

Worms captured Weinstock's imagination and that of his collaborator, David Elliott of the University of Iowa, because worm infections appear to regulate the immune system so that it functions normally. The allergic response - itchy, watery eyes, a runny nose and constriction of smooth muscles - evolved to flush out intestinal worms. "The immune system didn't evolve for allergy," Weinstock says. "Why in a hundred billion years of evolution would we evolve a response for allergy?"

In fact, says Robert Coffman, vice president of the biotech firm Dynavax Technologies, the immune system developed two sets of responses: one for bacteria and viruses and one for worms. Called Th1 for germs and Th2 for worms, they work in opposition. When Th1 is active, Th2 takes a break. When Th2 is active, it's Th1's turn. All of the symptoms people link with allergy are part of the Th2 response.

The worm turns

Weinstock, Elliott and other researchers believe that a low-grade infection with intestinal worms - pig whipworms because they can't reproduce in people - can restore the immune system's natural balance. A small-scale study in which 29 people with Crohn's disease drank whipworm eggs in Gatorade found that 23 responded to treatment and 21 of the 23 experienced complete remission.

Although worms haven't been directly tested in allergic patients, researchers point to a study by Maria Yazdanbakhsh of Leiden University in the Netherlands, which found that treating schoolchildren in Gabon for worms, so that the worms were expelled from their bodies, doubled their risk of becoming allergic to house dust mites, a common allergen.

Weinstock argues that it is exposure to the worms in the environment that confers protection against allergies. "That's one possibility," he says. "Whether it's due to worms, endotoxin, lifestyle, smoking or other factors that we haven't identified - that's the fun of it. But environment clearly plays a part."