How stress weakens immunity

Researchers have identified a mechanism by which chronic stress weakens the immune system, putting people at greater risk of disease and, possibly, premature aging.

The finding comes from studying older caregivers who look after spouses with Alzheimer’s disease and other dementia. These men and women often undergo years of stress, depression and social isolation, becoming physically and emotionally spent from a lack of adequate sleep, exercise and proper nutrition.

Researchers found that these caregivers have unusually high levels of a protein in the body called interleukin-6, or IL-6, which normally triggers inflammation to help fight infections. High levels of IL-6 are associated with cardiovascular disease, depression, osteoporosis, arthritis, Type 2 diabetes and some cancers. IL-6, for example, promotes the production of C-reactive protein, high levels of which are considered powerful predictors of heart attack risk.

Age alone raises levels of IL-6, but stress makes those levels rise even higher, the new study shows.

One potential effect of prolonged high levels of IL-6 is a “permanently aged immune response,” said lead study author Janice K. Kiecolt-Glaser, a professor of psychology and psychiatry at the Ohio State University College of Medicine. This likely occurs not just among caregivers, she said, but also among people who have experienced chronic severe stress for several years.

Kiecolt-Glaser and her husband, Ronald Glaser, a viral immunologist at Ohio State University, headed a research team from Ohio State and the University of North Carolina at Chapel Hill that monitored blood levels of IL-6 in 119 elderly caregivers and 106 non-caregivers (their average age was 70), for six years.

The study, released June 30 in the online version of the Proceedings of the National Academy of Sciences, found the average increase of IL-6 among the caregivers was four times higher than the increase measured in non-caregivers. Even three years after some of the caregivers’ spouses died, their IL-6 levels remained elevated.

The study makes “a very important contribution” because it begins to explain “the stress-biology connection, how stress gets translated into physical changes in the body, with the end result illness and sometimes mortality,” said Richard Schulz, director of the Center for Social and Urban Research at the University of Pittsburgh. He was lead author of a 1999 study published in the Journal of the American Medical Assn. that found caregivers had a 63% higher mortality rate during the study period than did non-caregivers. Schulz said the IL-6 finding explains some of what he and his colleagues speculated about. But he said it’s one of many potential mechanisms linking stress to illness and death.

When it comes to therapies that might protect the immune system from the ravages of stress, Kiecolt-Glaser pointed out that antidepressants lower IL-6 levels in chronically depressed patients, so they might be useful. She also said there have been suggestions that cholesterol-lowering statins might reduce IL-6, because they seem to reduce inflammation.

Some common lifestyle changes that people find difficult to adopt, such as regular exercise, can lower IL-6, while “all the bad behaviors you do when you’re stressed,” such as smoking and skimping on sleep, can increase IL-6, she said. So, too, can overeating, because fat cells secrete IL-6.

But while simple stress-reduction steps might make the biggest difference, “they may or may not be possible” for people to adopt, she acknowledged.