IT’S Saturday night. A brawl has broken out in a nightclub and men are
throwing punches, beer glasses and bar stools. There’s broken glass everywhere.
Later, these victims of testosterone-fuelled aggression will find their way to
the emergency room of the nearest hospital to get their wounds cleaned and
dressed. But the same surge of testosterone that brought them to blows may
already be helping to heal their injuries and prevent fatal infections.
That, at least, is the assertion of animal-behaviour expert Stan Braude from
Washington University in Saint Louis, Missouri. Other biologists may take some
persuading, not least because the orthodoxy is that testosterone increases our
susceptibility to infection. But Braude isn’t just threatening to turn
evolutionary theory on its head. His insight into the immune system may have
very practical implications for improving wound healing, and treating conditions
such as psoriasis and rheumatoid arthritis.
The story begins in the mid-1990s, when all the evidence seemed to show that
stressful life events lead to illness and elevated levels of the stress hormones
corticosterone and adrenalin. One young immunologist, Firdaus Dhabhar from the
Rockefeller University in New York, simply couldn’t accept that stress always
damages health, and in particular the immune system. “It really began to bother
me,” he says. “Stress is an intrinsic part of life and so it doesn’t make sense
that every time an organism is under stress it just suppresses its immune system
until it eventually caves in. Everything in physiology is designed to increase
and enable survival.”
Advertisement
Anthropologist Robert Sapolsky of Stanford University tackled the same
conundrum in his 1994 book Why Zebras Don’t Get Ulcers. He argued that
a brief burst of stress hormones provides a zebra with the fuel it needs for a
“fright and flight” response to the danger of an approaching lion. If it weren’t
for modern humans’ relatively sedentary yet stressful lifestyle, he said, stress
hormones wouldn’t be associated with illness—which is why zebras don’t get
ulcers but we do. This evolutionary explanation appealed to Dhabhar and he
decided to follow it up.
He chose to take a closer look at the normal mammalian response to a short
period of stress—the sort of acute stress that our African ancestors would
have needed to cope with. Until then, all the research suggested that such
stress results in a drop in the numbers of the immune system’s white cells
circulating in the blood. But Dhabhar’s experiments with rats revealed something
more. While white cell numbers in the blood do drop, they increase in the skin.
And once the stress is over, their distribution returns to normal. He fingered
the stress hormones corticosterone and adrenalin in these changes.
Braude was particularly drawn to the idea because he realised it could
explain the puzzling observation that, in the wild, male animals often have many
more gut parasites and other infections than females. The usual explanation is
that this is the result of immunosuppression by testosterone, a steroid hormone
with a similar chemical composition to stress hormones. This was thought to be
the price macho males pay for their dominance—an example of what
evolutionary biologists call the handicap principle. But Braude realised that if
testosterone redirects immunological effort to an animal’s surface, in the same
way that stress hormones do, high levels of the hormone could provide a direct
evolutionary benefit.
His theory also predicts that testosterone levels will tend to rise during
fights between rival males, priming the immune system to combat infections and
prevent their spread. There is some evidence that human males experience such a
hormonal surge. It probably also occurs in socially dominant baboons. And in
male birds, testosterone levels rise sharply during the mating season and may
fluctuate. But firm evidence for testosterone rushes is fragmentary, especially
in wild animal populations, where it is difficult to collect blood and urine
samples to test.
“It’s a really interesting hypothesis but it needs to be tested,” says
Dhabhar, who is now at Ohio State University. “The general idea is quite
appealing,” agrees Sapolsky. But sceptics point out that testosterone is only
part of a much bigger picture in which the benefits or otherwise of any one
hormone are still largely unknown. “The nature and strength of the immune
response change with any hormone—oestrogen, testosterone, thyroid hormone
and insulin all interact with the immune response and change how it’s going to
react to a foreign antigen or bacterium,” says Esther Sternberg, who heads the
neuroendocrine, immunology and behaviour section at the National Institute of
Mental 91ɫƬ in Bethesda, Maryland.
Braude admits it may all be coincidence. Testosterone may simply be
responsible for driving the aggressive behaviour that sparks a rise in stress
hormones, which in turn cause immunoredistribution. Despite this—and a
lack of funding—results from his latest research encourage him to continue
investigating the healing effects of testosterone. His preliminary, unpublished
results reveal that injecting mice with either testosterone or corticosterone
boosts their ability to fight off skin infections of Staphylococcus
aureus, the bacterium that often becomes resistant to antibiotics in
hospitals. And he has found that both hormones reduce healing times for skin
wounds in the ear, from about five days to four days.
While Braude’s ideas about the immune effects of testosterone have met with
some strong opposition, Dhabhar’s immunoredistribution theory—which
focuses on stress hormones instead—is slowly gaining ground. Ulrich von
Andrian from Harvard University, who studies the passage of white cells from the
blood into different body tissues, says it is possible that stress hormones
could redirect them, though we don’t yet know how. “[This] is forcing people to
rethink the whole subject,” adds Sapolsky.
Sternberg strongly supports the notion that stress is not all bad. Over a
decade ago, she showed that Salmonella quickly kills lab animals whose
stress hormones have been eliminated. “You need a balance,” she says.
Engineering such a balance may be the key to realising the practical potential
of this research. Chronic stress is known to increase the time that wounds take
to heal. So, before you can manipulate stress hormones to optimise wound
healing, you need to know more about the different physiological responses that
result from chronic and acute stress.
To that end, Dhabhar is studying patients who are about to undergo knee
surgery. He is monitoring their stress-hormone levels and the state of their
immune systems before the operation to see how stress might affect wound
infection and healing afterwards. “These studies give us an ability to
understand how we might harness the body’s natural abilities to up or
down-regulate immune function—to do what is most beneficial to the patient
at hand,” says Dhabhar.
He also hopes that insights into the link between stress and immunity may one
day improve treatments for autoimmune diseases such as psoriasis and rheumatoid
arthritis. Other groups that may benefit, says Braude, are chemotherapy
patients, whose wounds heal particularly slowly, and people with diabetes who
have poor blood flow to the skin and suffer potentially life-threatening skin
infections. “If something practical comes out of this I think that will be
evidence that taking an evolutionary approach is worthwhile,” he says.
