Outline of Opening Ceremony Talk

Does Stress Make You Sick and Believing Make You Well? The Science Connecting Body and Mind

Esther M. Sternberg M.D., National Institutes of Health, Bethesda, MD, USA.

The notion that stress makes you sick and believing makes you well has been part of the popular culture for thousands of years. These ideas are universal throughout all cultures. In Western culture these beliefs held sway from before the time of Hippocrates, when the Greeks built temples to Aesclepius, the God of healing, all the way through to modern times, when Norman Cousins and Norman Vincent Peale espoused the idea that laughter and positive thinking heals. Perhaps because these ideas were so much a part of the popular culture most scientists have until very recently rejected the concept that emotions can affect disease and that disease can affect our emotional health. In part this may be because until recently, scientists have not had the technological tools to prove these connections. But, in the last decade we have finally developed the technology in immunology and neuroscience to prove that these connections between emotions and disease, between the brain and the immune system, the mind and the body, are real.

Thus, with molecular biology we can prove that immune molecules, the interleukins, signal the brain through many routes - through the blood stream and through nerve pathways. And we can prove that when the brain receives such signals we experience a set of feelings and behaviors that, lumped together, are called "sickness behavior". We know that immune molecules can also stimulate the brain's hormonal stress response and start a cascade of hormones that finally result in the adrenal glands' release of anti-inflammatory corticosteroid hormones. Thus, the brain's stress response keep the immune system tuned down when an immune response is no longer needed to fight off a foreign invader. This can be good or bad, for too much of these anti-inflammatory stress hormones at the wrong time, such as during chronic stress, can predispose a stressed host to more infection. On the other hand, too little can predispose to autoimmune diseases such as arthritis, since the immune response is not shut off and can go on unchecked. Many studies have now proven that a blunted hormonal stress response in animals and humans, whether present on a genetic basis, because of drug therapy or because of surgical intervention, can all lead to increased susceptibility to inflammatory disease. These diseases include arthritis, systemic lupus erythematosus, allergic asthma and atopic dermatitis. Knowing this can help treat such diseases, or can lead to development of new treatments for such illnesses based on stimulating various parts of the hormonal stress response.

But immune molecules, the interleukins do not simply act as hormones to stimulate brain function. They also act as growth factors when expressed in brain. These molecules are made by the scaffolding cells in the brain - those cells that are not nerve cells that provide an essential milieu to help nerve cells survive or kill them off. So through this science we know that interleukins play an important role in nerve cell death and survival and therefore in nerve regeneration and repair. Thus, interactions between the immune and nervous system play a role in diseases such as Alzheimer's, stroke, neuroAIDS and nerve trauma. Understanding exactly how such molecules and immune cells interact with nerve cells is helping us develop new treatments for these diseases. Interactions in the other direction are also true - that is, nerve chemicals play a role in keeping the immune system active. In this way, adrenalin-like molecules released from nerve endings in the spleen can help restore lost immune cell function that occurs during aging. Drugs which stimulate growth of such nerve endings can thus be used to enhance the diminished immune responses seen in aging. There are still more communications between these systems that occur at a local level, where nerve endings feed tissues, such as the lining of joints. Nerve chemicals released from such nerve endings during inflammation can increase inflammation, and thus drugs that block such nerve chemicals can be used to treat arthritis.

What does the future hold? All of these discoveries just touch the surface, and each leads to many more questions, which when answered in depth will lead to more specific ways to manage stress effects on immune function, local effects of nerve chemicals on inflammation, effects of immune molecules on nerve growth and death. Studies showing the effects of interleukins on sickness behavior raise the question whether these molecules play a role in illnesses such depression, in the absence of infection. We now have the tools to answer these questions by combining molecular biology and modern imaging technologies. With such technologies we should also be able to take studies of the effects of stress on immune responses to the next level, by asking how learning and memory and early experience and development affect the stress response. With sophisticated new genetic and mathematical modeling techniques, we can determine what part of our stress responsiveness we are born with, and how much is under environmental control. These sorts of studies will help us understand not only the reasons for individual differences in stress responsiveness that affect susceptibility to inflammatory disease, but will also point the way to using old and developing new behavioral strategies that can change the set point of different individual's stress responses. So this science can help explain why meditation, crystals or other alternative therapies do work to ameliorate disease. By studying the neurobiology of the placebo effect, we can not only understand such phenomena that have been around for thousands of years in all cultures, but physicians can also shed the bias that has stigmatized the lowly placebo effect, and rather than trying to control for it and exclude it, can use this very powerful biological effect judiciously to help heal.

More than anything else this field of neuroimmunomodulation - the brain-immune connection, the science of the mind-body connections, embodies the marriage of the beliefs of the popular culture with technological advances across many disciplines, from the molecular through to the systems interaction levels. That is the most important contribution of this field to modern science and medicine - it pushes and pulls science out of a narrow reductionist view rooted in the 16th century philosophy of Descartes, back into the holistic view of body and soul entwined, embodied by Hippocrates. But it does so with a modern technological twist that empowers us to apply this science to discover new treatments for a whole host of diseases.

So, this very old science, born before recorded history, has now, with modern scientific technology been reborn. Not only can this science help physicians and scientists believe their patients when they say that stress makes them sick and believing makes them well, but it can help us develop new therapies to treat many diseases, from arthritis to Alzheimers' and stroke, from nerve trauma to the immunosuppression of aging.

traduction français

Dernière mise à jour : dimanche 26 mars 2000 19:24:49

Dr Jean-Michel Thurin

Stress Immunité