New Light Shed on Brain-Immune System Link

Researchers reported here Monday the first evidence suggesting how the brain can physically interact with the immune system to alter the course of diseases.

The discoveries provide experimental support for previous observations that stress and depression can make individuals more susceptible to disease, whereas a positive attitude can help fight disease.

One group from the University of Rochester reported that some neurons in the central nervous system make direct contact with white blood cells through special receptors in various organs. The researchers assume that changes in immune functioning can be stimulated through this connection, although that has not yet been proven. The link may also signal the status of the immune system to the brain.

Another group, from the University of Chicago, reported that some brain cells can produce an important chemical mediator of immune function called interleukin-1 (IL-1). It has long been known that brain cells respond to IL-1, but not that they can actually produce it.

The discoveries provide new insights into the role of the brain in disease. It may also lead to new ways to manipulate the immune system, either to boost it to help fight disease or to suppress it to prevent transplant rejection.

“We now have a whole new class of drugs--neuroactive agents--that can be explored to suppress the immune system,” said Dr. David L. Felten, a neurologist at Rochester.

Epidemiological and anecdotal evidence have long suggested a link between emotions and disease. Studies have shown that depression, bereavement and stress can all impair immune function and increase susceptibility to disease.

Classic studies at Ohio State University, for example, showed that medical students have the greatest amount of illness and the most days absent during periods of greatest stress in their curriculum, such as during final examinations. Other studies have shown that women treated for breast cancer are more likely to have a recurrence of the disease if they suffer from depression after treatment.

But the mechanisms by which the brain could affect the immune system have remained a mystery. The new discoveries shed the first light on how that process occurs.

Felten, his wife, neurobiologist Suzanne Felten, and their colleagues at Rochester have discovered receptors in bone marrow, lymph nodes, the spleen and the lining of blood vessels from rodents and primates that are directly connected to the central nervous system. Studies showed that white blood cells moving through these organs and the circulatory system connect briefly with these receptors, then continue their movements.

“This is the first demonstration of innervation (links to the nervous system) of mobile cells,” David Felten said. The purpose of the nerve connections to white cells is not yet known. He speculates that the link may provide not only a way for the brain to stimulate the immune system, but also for it to learn the status of the immune system.

“The link that has been missing so long (in studies of immunity and emotions) was communication back to the brain,” he said. These nerves could provide it.

Two-way communication between the brain and the immune system could also be provided by IL-1, said Dr. Clifford B. Saper, a pharmacologist in Chicago. Researchers already knew that IL-1 secreted by white blood cells could affect the brain. Now it appears that IL-1 secreted by the brain can also affect the immune system.

IL-1 is produced in white blood cells in response to an infection. It causes other white blood cells to make disease-fighting proteins and “turns on” T-lymphocytes, which can destroy invading bacteria.

It also acts on the brain, causing the release of hormones that produce fever, sleepiness, headaches and muscle aches--all byproducts of the body’s fight against invaders. IL-1 “is why you feel the way you do when you are sick,” Saper said.

Using tissues from human cadavers, Saper has found that IL-1 is produced in certain parts of the brain and the peripheral nervous system as well as in white blood cells. This discovery, he said, suggests the existence of a “feedback loop” between the brain and the immune system by which the brain controls stability of the immune system in the face of an outside challenge. In other words, the brain keeps the immune system from overreacting and damaging body tissues.

Together, the new studies provide a foundation for further research on the interconnection of the brain and the immune system. Felten concluded: “Finally we can put real biochemical links together to get at the roots of psychosomatic disease.”