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Seasonal cool spurs resistance to disease Hormone may brace immune system for winter onslaught

THE BALTIMORE SUN

Seasonal cycles are known to influence everything from the sex lives of horses to the migration patterns of birds. Now a Johns Hopkins University researcher says that autumn's lengthening nights may trigger another important change: mobilizing the disease-fighting immune systems of various creatures, including humans, to face the onslaught of winter.

The body appears to do this, said Randy J. Nelson, a professor of psychology at Hopkins, on cue from a hormone called melatonin. And to explain how this versatile chemical became a kind of seasonal alarm system, Dr. Nelson turns to no less an authority than Charles Darwin and his theory of evolution.

"It's well known that people and animals get sick more often in the winter than the summer" because of a variety of stresses, said the Hopkins researcher, who specializes in studying the effects of hormones on behavior in animals, particularly prairie voles.

"What we suggest is that it would be even worse if the melatonin wasn't working to counteract these stressors."

Medical researchers in recent years have studied using doses of melatonin as way to treat insomnia, cure jet lag, prevent pregnancy and protect the body from naturally produced chemicals called free radicals. It has been tested as a therapy for various cancers and scores of other diseases, many of them linked to aging.

Available in health food stores as a nutritional supplement, without a prescription, melatonin has suddenly blossomed as a hot health fad, the subject of glowing magazine articles and books.

It may be too early to sift the facts from the hype, and the landscape is littered with wonder drugs that weren't.

But there is no question that the hormone, produced by a tiny, pinecone-shaped structure in the brain called the pineal gland, plays an important role in the body's struggle against disease. And it may one day become an important therapy for a broad spectrum of diseases.

Over the past several years, scores of scientists, including Dr. Nelson, have tested melatonin to try to pin down what it does. Intrigued by the substance's broad range of effects, Dr. Nelson also began to wonder why it triggers them.

Now, in a draft paper under review by the Journal of Pineal Research, he and three co-authors suggest an explanation right out of Darwin's "Origin of Species."

Darwin saw things this way: Natural selection has, through much trial and more error, written our collective genetic code over the past four million years or so. That code equips us to survive, and -- what is more important from the standpoint of our genes -- reproduce.

But for the past 100,000 years or so, humans haven't changed all that much. Our crafty species has dreamed up innovations, such as agriculture and tools, that help us outwit many of the brutal forces that drive evolution.

So while we do most of our hunting and gathering in supermarkets and malls, our gene-designed bodies, in general, still respond as though we were loping through the forest primeval.

Consider, then, life in a primitive environment as winter approaches. In most latitudes, the weather turns cold. Food gets scarce. Predators are hungry, too, so they take more risks and pursue prey more relentlessly. For prey, there is a lack of leafy cover to scurry beneath.

To cope with the physical demands of fight, flight or frenzied forage, animals release a class of steroids that enhance physical performance, but have several nasty side effects -- they can depress immune function and do long-term damage to tissues.

So for hundreds of thousands of years, the start of the cold weather, with its physical demands and hormonal assaults, has probably been the time of the year when the body is most vulnerable to marauding microbes. People still get sick more often in the winter.

So how's a body to cope?

Dr. Nelson suggests that evolution came up with an answer: melatonin. The gland that releases the hormone is exquisitely sensitive to changes in the length of the nighttime and in a number of animals serves as a kind of chemical calendar.

Here's how it works: After about four hours of darkness, the pineal gland, which is sensitive to signals from the retina, kicks in and starts to bathe the body in melatonin. It abruptly shuts off when the retina in the eye is stimulated by a bright light.

As the length of the night increases through the fall, so does our exposure to the hormone. Animals use this signal to keep track of the seasons, and help them pick the right time to molt, mate, migrate or hibernate, among other things.

In evolutionary terms, Dr. Nelson says, critters able to anticipate the annual stresses of winter and compensate by throttling up their immune systems would have had a crucial edge in the highly competitive business of staying alive, and having offspring.

Animals that couldn't cope with winter's harshness would tend to die young, leaving few or no offspring, their genetic blueprints tossed into nature's recycling bin.

That's the basic theory. What's the evidence for it?

First, Dr. Nelson points to a number of studies suggesting that periods of darkness boost the immune system.

In one study, a researcher kept laboratory rats in a dark room for four weeks straight. The animals experienced a 315 percent increase in the size of their thymus, part of the immune system responsible for processing disease-battling lymphocytes called T cells.

There is also evidence that melatonin itself beefs up the body's microbial defenses: in animal studies, when the pineal gland was removed or disabled, the creatures wound up with weakened immune systems. Immune function was restored with melatonin therapy.

Dr. Nelson, who holds doctorates in psychology and endocrinology from the University of California at Berkeley, admits he doesn't have all the answers.

He isn't sure, for example, precisely how melatonin might work. And he realizes his interpretation of the annual cycle of disease is not the only one.

"Is flu season related to people getting together and bundling up in close quarters?" he asked. "Or do we have reduced immune function, and so are more susceptible to bugs?" There is no conclusive evidence either way, he noted.

Randolph Nesse, director of the University of Michigan's Evolution and Human Behavior Program, and one of the founders of the small but growing field of Darwinian medicine, said he was intrigued by Dr. Nelson's idea.

"It seems like an interesting and plausible idea that's worth testing," he said.

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