The stress connection
Modern medicine, which once treated the connection between emotions and physical health with skepticism, has come to appreciate the closely linked relationship of mind and body. A wide variety of maladies, including stomach upset, hives, and even heart disease, are linked to the effects of emotional stress. But although the relationship between stress and immune function is being studied by a number of different types of scientists, so far it is not a major area of research for immunologists.

Studying the relationship between stress and the immune system presents difficult challenges. For one thing, stress is difficult to define. What may appear to be a stressful situation for one person is not for another. When people are exposed to situations they regard as stressful, it is difficult for them to measure how much stress they feel, and difficult for the scientist to know if a person’s subjective impression of the amount of stress is accurate. The scientist can only measure things that may reflect stress, such as the number of times the heart beats each minute, but such measures also may reflect other factors.
Most scientists studying the relationship of stress and immune function, however, do not study a sudden, short-lived stressor; rather, they try to study more constant and frequent stressors known as chronic stress, such as that caused by relationships with family, friends, and co-workers, or sustained challenges to perform well at one’s work. Some scientists are investigating whether ongoing stress takes a toll on the immune system.
But it is hard to perform what scientists call “controlled experiments” in human beings. In a controlled experiment, the scientist can change one and only one factor, such as the amount of a particular chemical, and then measure the effect of that change on some other measurable phenomenon, such as the amount of antibodies produced by a particular type of immune system cell when it is exposed to the chemical. In a living animal, and especially in a human being, that kind of control is just not possible, since there are so many other things happening to the animal or person at the time that measurements are being taken.
Despite these inevitable difficulties in measuring the relationship of stress to immunity, scientists who repeat the same experiment many times with many different animals or human beings, and who get the same result most of the time, hope that they can draw reasonable conclusions.
Some researchers place animals into stressful situations, such as being trapped in a small space or being placed near an aggressive animal. Different functions of their immune systems, and their health, are then measured under such stressful conditions. On the basis of such experiments, some published studies have made the following claims:
Experimentally created “stressful” situations delayed the production of antibodies in mice infected with influenza virus and suppressed the activity of T cells in animals inoculated with herpes simplex virus.
Social stress can be even more damaging than physical stress. For example, some mice were put into a cage with a highly aggressive mouse two hours a day for six days and repeatedly threatened, but not injured, by the aggressive mouse — a “social stress.” Other mice were kept in tiny cages without food and water for long periods — a “physical stress.” Both groups of mice were exposed to a bacterial toxin, and the socially stressed animals were twice as likely to die.
Isolation can also suppress immune function. Infant monkeys separated from their mothers, especially if they are caged alone rather than in groups, generate fewer lymphocytes in response to antigens and fewer antibodies in response to viruses.
Many researchers report that stressful situations can reduce various aspects of the cellular immune response. A research team from Ohio State University that has long worked in this field suggests that psychological stress affects the immune system by disrupting communication between the nervous system, the endocrine (hormonal) system, and the immune system. These three systems “talk” to one another using natural chemical messages, and must work in close coordination to be effective. The Ohio State research team speculates that long-term stress releases a long-term trickle of stress hormones — mainly glucocorticoids. These hormones affect the thymus, where lymphocytes are produced, and inhibit the production of cytokines and interleukins, which stimulate and coordinate white blood cell activity. This team and others have reported the following results:
Elderly people caring for relatives with Alzheimer’s disease have higher than average levels of cortisol, a hormone secreted by the adrenal glands and, perhaps because of the higher levels of cortisol, make fewer antibodies in response to influenza vaccine.
Some measures of T cell activity have been found to be lower in depressed patients compared with nondepressed patients, and in men who are separated or divorced compared with men who are married.
In a year-long study of people caring for husbands or wives with Alzheimer’s disease, changes in T cell function were greatest in those who had the fewest friends and least outside help.
Four months after the passage of Hurricane Andrew in Florida, people in the most heavily damaged neighborhoods showed reduced activity in several immune system measurements. Similar results were found in a study of hospital employees after an earthquake in Los Angeles.
In all of these studies, however, there was no proof that the immune system changes measured had any clear adverse effects on health in these individuals.
Does being cold make you sick?
Almost every mother has said it: “Wear a jacket or you’ll catch a cold!” Is she right? So far, researchers who are studying this question think that normal exposure to moderate cold doesn’t increase your susceptibility to infection. Most health experts agree that the reason winter is “cold and flu season” is not that people are cold, but that they spend more time indoors, in closer contact with other people who can pass on their germs.
But researchers remain interested in this question in different populations. Some experiments with mice suggest that cold exposure might reduce the ability to cope with infection. But what about humans? Scientists have dunked people in cold water and made others sit nude in subfreezing temperatures. They’ve studied people who lived in Antarctica and those on expeditions in the Canadian Rockies. The results have been mixed. For example, researchers documented an increase in upper respiratory infections in competitive cross-country skiers who exercise vigorously in the cold, but whether these infections are due to the cold or other factors — such as the intense exercise or the dryness of the air — is not known. They’ve found that exposure to cold does increase levels of some cytokines, the proteins and hormones that act as messengers in the immune system, but how this affects health isn’t clear.
A group of Canadian researchers that has reviewed hundreds of medical studies on the subject and conducted some of its own research concludes that there’s no need to worry about moderate cold exposure — it has no detrimental effect on the human immune system. Should you bundle up when it’s cold outside? The answer is “yes” if you’re uncomfortable, or if you’re going to be outdoors for an extended period where such problems as frostbite and hypothermia are a risk. But don’t worry about immunity.
Exercise: good or bad for immunity?
Regular exercise is one of the pillars of healthy living. It improves cardiovascular health, lowers blood pressure, helps control body weight, and protects against a variety of diseases. But does it help maintain a healthy immune system? Just like a healthy diet, exercise can contribute to general good health and therefore to a healthy immune system. It may contribute even more directly by promoting good circulation, which allows the cells and substances of the immune system to move through the body freely and do their job efficiently.
Some scientists are trying to take the next step to determine whether exercise directly affects a person’s susceptibility to infection. For example, some researchers are looking at whether extreme amounts of intensive exercise can cause athletes to get sick more often or somehow impairs their immune function. To do this sort of research, exercise scientists typically ask athletes to exercise intensively; the scientists test their blood and urine before and after the exercise to detect any changes in immune system components such as cytokines, white blood cells, and certain antibodies. While some changes have been recorded, immunologists do not yet know what these changes mean in terms of human immune response. No one yet knows, for example, whether an increase in cytokines is helpful or has any true effect on immune response. Similarly, no one knows whether a general increase in white cell count is a good thing or a bad thing.
But these subjects are elite athletes undergoing intense physical exertion. What about moderate exercise for average people? Does it help keep the immune system healthy? For now, even though a direct beneficial link hasn’t been established, it’s reasonable to consider moderate regular exercise to be a beneficial arrow in the quiver of healthy living, a potentially important means for keeping your immune system healthy along with the rest of your body.
One approach that could help researchers get more complete answers about whether lifestyle factors such as exercise help improve immunity takes advantage of the sequencing of the human genome. This opportunity for research based on updated biomedical technology can be employed to give a more complete answer to this and similar questions about the immune system. For example, microarrays or “gene chips” based on the human genome allow scientists to look simultaneously at how thousands of gene sequences are turned on or off in response to specific physiological conditions — for example, blood cells from athletes before and after exercise. Researchers hope to use these tools to analyze patterns in order to better understand how the many pathways involved act at once.
Source: Harvard Health Publications, Harvard Medical School