Researcher Explains Stress-Inflammation Link
Janice Kiecolt-Glaser, Ph.D.
Stress is an everyday fact of life for most people. It is becoming common knowledge, however, that stress at too-high "doses," and/or for too-long periods of time, can cause health problems. Janice Kiecolt-Glaser, Ph.D., an NCCAM-funded researcher, discussed "How Stress Kills: New Perspectives on Stress and Inflammation" in a lecture at NIH on May 9, 2008, in Bethesda, Maryland.
Dr. Kiecolt-Glaser is well known for her research contributions to psychoneuroimmunology—an interdisciplinary field that studies the relationships among the endocrine system, the nervous system, and the immune system, and how those relationships affect health. She holds the S. Robert Davis Chair of Medicine at the Ohio State University College of Medicine, where she is also professor of psychiatry and psychology and director of the Division of Health Psychology in the Department of Psychiatry. Dr. Kiecolt-Glaser is a member of the National Academy of Sciences.
Cytokine Levels Are Key
Our bodies respond to infection or trauma by mounting an inflammatory response, Dr. Kiecolt-Glaser explained in her opening remarks. Part of this response is the release of proinflammatory cytokines—proteins that attract immune cells to injuries and turn on their healing response. But when a person has a level of proinflammatory cytokines that is chronically high—as from a chronic or recurring infection or wound (such as a "fist-sized wound in the mouth" called gum disease, or repeated urinary tract infections)—the risk for getting certain age-related diseases and conditions goes up, too, including:
- Cardiovascular disease (heart disease and stroke)
- Type 2 diabetes
- Osteoporosis
- Arthritis
- Some cancers
- Frailty and functional decline.
The most likely culprit is a specific type of proinflammatory cytokine, interleukin 6 (IL-6).
The connection with stress? In a nutshell, stress, too, can raise the production of proinflammatory cytokines—substantially, and when such an increase is not biologically called for. Acute stress can provoke a temporary increase in levels of these cytokines, chronic stress a longer one. Some other factors that drive them up are the aging process, depressive symptoms, and clinical depression. In a double whammy, each also decreases the production of proinflammatory cytokines in places where they are most needed—the sites of wounds and infections.
A chain of events that begins with stress and/or depression can lead to increased production of proinflammatory cytokines, thus raising the risk for certain diseases and conditions linked to inflammation. Step 4 can lead back to Step 1, thereby increasing stress and depression and potentially creating a cycle.
© Janice Kiecolt-Glaser, Ph.D., used by permission
Dementia Caregiving as a Stressor
Dr. Kiecolt-Glaser discussed her work in some models of states of stress. One consists of caregiving spouses of people who have a progressive dementia disease, such as Alzheimer's disease. This caregiving is "an important and chronic stressor that takes a large toll on the body," she said. "It is, actually, a process of living bereavement."
Her team has found lowered immune function and impaired wound healing in study groups of these caregivers. In one study, when given a flu shot, the caregivers had poorer antibody and virus-specific T-cell responses to the shot than did a control group of noncaregivers. This difference widened significantly after age 70. Lowered immunity—and a vulnerability to depression and loneliness—persisted for caregivers for up to 3 years after their ill spouse had died and their caregiving burden had ended. In another study in this population, caregivers took about 24 percent longer than noncaregiving controls to heal a minor puncture wound.
Dr. Kiecolt-Glaser believes that chronic stressors may "prematurely age" the immune response. "Age interacts with stress," she said. "The older you are, the more that stress really matters."
Other Stressed Populations
Dr. Kiecolt-Glaser has observed similar effects in other groups, too. For example, her team administered a small puncture wound to a group of dental school students, doing so once during an exam period and then again during a vacation period. They examined how the wounds healed. All the students took longer (on average, 3 days longer) to heal their wounds during exams than during vacation; the researchers attribute this to stress. An earlier study in medical students of their response to a hepatitis B vaccine also found indications of lower immune function during exam periods.
"If you're wounded and you're stressed," Dr. Kiecolt-Glaser commented, "you take longer to heal. You also have a greater chance of infection."
Looking At Other Factors
Dr. Kiecolt-Glaser also discussed the link between stress, proinflammatory cytokines, inflammation, and a number of other health factors:
- Symptoms of depression: In some studies, major depression has been found to be associated with increased secretion of these cytokines, and depressive symptoms with increased levels of IL-6.
- Sleep problems: Being deprived of sleep alters the body's secretion of IL-6 by night and day, throwing off the immune system and decreasing the sense of well-being.
- Health behaviors: Certain health-compromising behaviors—such as eating a higher-fat diet, getting less exercise, and smoking—have been found to increase IL-6 levels.
- Fatty acids: People's intake of omega-3 and omega-6 fatty acids, including the ratios at which they take them, is an intriguing area, Dr. Kiecolt-Glaser said, and may reflect in part certain historical changes in the American diet.
Currently, Dr. Kiecolt-Glaser is conducting two studies with NCCAM support investigating the effects of omega-3 supplementation and of selected hatha yoga postures traditionally used for the immune system and general restoration; both studies are looking at measures related to stress and well-being.
Dr. Kiecolt-Glaser also conducts other NIH-sponsored research. Her May 9 lecture was sponsored by the National Institute on Dental and Craniofacial Research.
Selected References
- Glaser R, Kiecolt-Glaser JK. Stress-induced immune dysfunction: implications for health. Nature Reviews: Immunology. 2005;5(3):243–251.
- Kiecolt-Glaser JK, Glaser R, Gravenstein S, et al. Chronic stress alters the immune response to influenza virus vaccine in older adults. Proceedings of the National Academy of Sciences of the United States of America. 1996;93(7):3043–3047.
- Kiecolt-Glaser JK, Marucha PT, Malarkey WB, et al. Slowing of wound healing by psychological stress. Lancet. 1995;346(8984):1194–1196.
- Marucha PT, Kiecolt-Glaser JK, Favagehi M. Mucosal wound healing is impaired by examination stress. Psychosomatic Medicine. 1998;60(3):362–365.
- Glaser R, Kiecolt-Glaser JK, Bonneau RH, Malarkey W, Kennedy S, Hughes J. Stress-induced modulation of the immune response to recombinant hepatitis B vaccine. Psychosomatic Medicine. 1992 Jan-Feb;54(1):22–9. PMID: 1553399
