The Scientific Journals

By : Esther M. Sternberg and Philip W. Gold

In the past, the association between an inflammatory disease and stress was considered by doctors to be secondary to the chronic pain and debilitation of the disease. The recent discovery of the common  underpinning of the immune and stress responses may provide an explanation of why a patient can be  susceptibleto both inflammatory disease and depression. The hormonal dysregulation that underlies both inflammatory disease and depression can lead to either illness, depending on whether the perturbing stimulus is pro-inflammato- ry or psychologically stressful. That may explain why the waxing and waning of  depression  in arthritic patients does not always coincide with inflammatory flare-ups.

The popular belief that stress exacerbates inflammatory illness and that relaxation or removal of stress ameliorates it may indeed have a basis in fact. The interactions of the stress and immune systems and the hormonal responses they have in common could explain how conscious attempts to tone down responsivity to stress could affect immune responses.

IMMUNE SIGNALS TO THE BRAIN via the bloodstream can occur directly or indirectly. Immune cells such as monocytes, a type of white blood cell, produce a chemical messenger called interleukin- 1 (IL-1), which ordinarily will not pass through the blood-brain barrier. But certain cerebral blood vessels contain leaky junctions, which allow IL-1 molecules to pass into the brain. There they can activate the HPA axis and other neural systems. IL-1 also binds to receptors on the endothelial cells that line cerebral blood vessels. This binding can cause enzymes in the cells to produce nitric oxide or prostaglandins, which diffuse into the brain and act directly on neurons.

How much of the responsivity to stress is genetically determined and how much can be consciously controlled is not known. The set point of the stress response is to some extent genetically determined. An event that is physiologically highly stressful to one individual may be much less so to another, depending on each person’s genetic tendency to hormonal reactivity. The degree to which stress could precipitate or
exacerbate inflammatory disease would then depend both on the intensity of the stressful stimulus and on the set point of the stress system.

Psychological stress can affect an individual’s susceptibility to infectious diseases. The regulation of the immune system by the neurohormonal stress system provides a biological basis for understanding how stress might affect these diseases. There is evidence that stress does affect human immune responses to viruses and bacteria. In studies with volunteers given a standard dose of the common cold virus (rhinovirus), individuals who are simultaneously exposed to stress show more viral particles and produce more mucus than do nonstressed individuals. Medical students receiving hepatitis vaccination during their final exams do not develop full protection against hepatitis. These findings have important implications for the scheduling of vaccinations. People who are vaccinated during periods of stress might be less likely to develop full antibody protection.

Animal studies provide further evidence that stress affects the course and severity of viral illness, bacterial disease and septic shock. Stress in mice worsens the severity of influenza infection and affects both the HPA  axis and the sympathetic nervous system. Animal studies suggest that neuroendocrine mechanisms could play  a similar role in infections with other viruses, including HIV, and provide a mechanism for  understanding clinical observations that stress may exacerbate the course of AIDS. Stress increases the  susceptibility of mice to infection with mycobacteria, the bacteria that causes tuberculosis. It has been shown that an intact HPA axis protects rats against the lethal septic effects of salmonella bacteria. Finally, new understanding  of interactions of the immune and stress responses can help explain the puzzling observation that classic psychological conditioning of animals can influence their immune responses. For example, working with rats, Robert Ader and Nicholas Cohen of the University of Rochester paired saccharinflavored water with an  immunosuppressive drug. Eventually the saccharin alone produced a decrease in immune function similar to  that of the drug.

Stress is not only personal but is perceived through the prism of interactions with other persons. Social  interactions can either add to or lessen psychological stress and similarly affect our hormonal responses to it,  which in turn can alter immune responses. Thus, the social psychological stresses that we experience can  affect our susceptibility to inflammatory and infectious diseases and the course of a disease. For instance, studies have shown that persons exposed to chronic social stresses for more than two months have increased  susceptibility to the common cold.

Other studies have shown that the immune responses of long-term caregivers, such as spouses of Alzheimer’s patients, become blunted. Immune responses in unhappily married and divorcing couples are also blunted.  Often the wife has a feeling of helplessness and experiences the greatest amount of stress. In such a scenario,  studies have found that the levels of stress hormones are elevated and immune responses usually are lowered  in the wife but not in the husband.

On the other hand, a positive supportive environment of extensive social networks or group psychotherapy  can enhance immune response and resistance to disease—even cancer. Women with breast cancer, for  instance, who receive strong, positive social support during their illness have significantly longer life spans than women without such support.

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