Testosterone, Stress May Not Suppress Immune System After All

Now a biologist at Washington University in St. Louis is suggesting a completely different role for the hormone that made John Travolta and John Wayne famous.

Stanton Braude, Ph.D., a lecturer in biology in Arts and Sciences, analyzed a number of studies that focused on the phenomenon whereby bright or showy male animals advertise their disease resistance. For instance, a male bird, during mating season, will display showy feathers to let females know that he is healthy -- resistant to parasites -- and would be a good mate. This evolutionary trick could be likened to Travolta gliding on the dance floor or the Duke strutting through a saloon to talk to the bar maid. These studies, however, revealed a paradox: testosterone, a long-assumed immunosuppressive, is also known to trigger the sexual display. How, Braude asked, could an immunosuppressive play such a vital role?

"The whole idea that testosterone and stress suppress the immune system makes absolutely no sense evolutionarily," says Braude. "Why would we have evolved to shut off immunity when that's so important to keep us healthy? I began to search for another mechanism for testosterone."

Braude came across a new body of research -- about a dozen studies in all over the past five years -- that questions the whole idea of immunosuppression and suggests that, instead of suppressing the immune system, testosterone and other steroids play a key role in what's called immunoredistribution.

"The redistribution hypothesis predicts that when you are under stress the total number of immune cells in your body remains the same but are sent where they are most useful -- to the skin to anticipate getting wounded and prevent infection," Braude explains. "This makes perfect sense from an evolutionary standpoint. Now, today, with people constantly stressed, those immune cells aren't protecting your gut from a virus or your lungs from an infection or a cold. So, you might get these illnesses, but the immune cells are out there protecting the skin. Personally, between gangrene and a cold, I'll take the cold."

Braude's new idea is that testosterone signals infection-fighting white blood cells to go out of the blood stream and into the skin. He says it's also possible that testosterone merely triggers the stress response, and other steroids from the adrenal gland then execute the redistribution.

"The bottom line is that a blood test of a highly parasitized breeding male peacock would show high testosterone but low white blood cell counts because the cells are temporarily out of the blood stream and in the skin," Braude says.

Why the skin?

Think of a wild animal or a human some 1,000 years ago and what their biggest health concern would be: Getting ripped to shreds by another human or animal.

Braude published his new testosterone immunoredistribution hypothesis in the June 1999 issue of Behavioral Ecology. He specifically analyzed three studies that tried to link testosterone and immunosuppression and countered them with the redistribution hypothesis. He also cited recent literature that indicated an association with testosterone and a healthy immune system in lizards, fowl and voles.

Defense mechanism

To understand why evolutionary biologists look at animals and sexual display, it's important to realize that before the days of the Hefner lifestyle, courtship and breeding were very stressful. They still are for male birds and mammals, which have higher levels of testosterone during breeding season, in part because of the thrill of the hunt but also because males have to fight other males to gain the favor of their preferred females. Males get more wounds during breeding season than any other time of the year. Braude and others think the high testosterone levels during breeding season may serve to prime the animals' immune systems to defend against a wound.

"The short take is that testosterone and stress have long been mistaken as suppressants when in fact they are a part of the process that redistributes white blood cells," says Braude. "I think the old theory about immunosuppression made a lot of sense on the surface. You can see it every day. If someone's stressed, they're likely to get sick. The simple interpretation is that the immune system is suppressed. But the redistribution hypothesis is more reasonable. It just doesn't make sense to suppress your immune system, even under stress."

Braude says redistribution has been extensively demonstrated in rats. And he points to a study by Firdauss Dhabbar, Ph.D., professor of biology at Rockefeller University, that shows that a variety of white blood cells return to normal levels in the blood stream three hours after an animal is stressed, suggesting that they leave the blood stream and go to the skin. While Dhabbar and Braude concede that large pharmacological doses of steroids can inhibit immune cells, they have shown that is not the case with normal levels of these hormones.

Braude is complementing Dhabbar's work by studying wounded mice to see how long it takes for them to heal after treatment with testosterone or other steroids. Preliminary results so far indicate that healing takes about one week, and animals given testosterone or other steroids heal a day sooner than untreated animals.

"I'm trying to show what hundreds of researchers for the past 20 years have mistaken," he says. "If all you do to measure immunity is count immune cells in a blood sample, you get the lower count because they are leaving the blood stream and going to the skin. But that doesn't mean that testosterone and steroids lower immunity. I'm interested in showing why this is useful from an evolutionary point of view."