By Avigayil Kadesh
People under constant stress are vulnerable to developing an auto-immune disorder, according to new research by Israeli Prof. Alon Monsonego of Ben-Gurion University of the Negev.
“My expertise is in neuro-immunology, a very exciting field where we try to understand the dialogue between the two systems,” says the professor. “We believe there is no neurological syndrome that has nothing to do with the immune system.”
Along with Dr. Idan Harpaz and Prof. Hagit Cohen, Monsonego characterized, for the first time, the mechanisms that cause damage to immune system regulation in mice exposed to chronic stress.
Their research, published in the European Journal of Immunology, analyzed what happens in the hypothalamic-pituitary-adrenal (HPA) axis that runs between the brain and the immune system.
When someone experiences acute stress, the HPA axis messages the adrenal glands to release the hormone cortisol in order to suppress the immune system temporarily.
“This is an essential response of the body to protect itself, a kind of biological feedback,” explains Monsonego. “The increased level of glucose [from cortisol] energizes you to face acute stress in seconds.”
However, in chronically stressed people -- such as caregivers or workaholics – low levels of cortisol are constantly coursing through their bloodstream. In time, the immune system begins to ignore the signal.
“The regulation control of the immune system becomes damaged and we get a more aggressive immune system in reaction,” says Monsonego. This is similar to the way antibiotics can lead to more aggressive “superbug” microbes.
“The stress causes immune suppression, but at the same time, the cells that survive [the suppression] become more aggressive and do not respond to increased cortisol.”
The mice in the Israeli lab were exposed to chronic stress for 24 days and then exposed to a disease that is the animal model for multiple sclerosis. Because of the excess cortisol, the scientists say, the mice were more prone to develop the disease than they were before.
Monsonego believes the same effect occurs in humans. “If the HPA axis is not functioning well, you’re more prone to autoimmune disease. Which one you develop depends on genetics and environment.”
The effect was more significant in female mice than in male mice. This may help explain the higher rates of autoimmune disease in women than in men.
Effect on Alzheimer’s patients and spouses
Monsonego and his collaborators are now studying how this phenomenon affects Alzheimer’s patients – who are stressed during the initial stage of disease as they recognize their progressive memory loss – as well as their spouses.
“We isolated immune cells from their blood and analyzed them,” says Monsonego, who soon hopes to publish the results.
“Another aspect of this story is that a similar mechanism can take place following chronic inflammation, such as arthritis. Triggering the inflammatory reaction triggers release of cortisol. It’s a basic mechanism that can affect many systems.”
The ultimate goal is devising a blood test to measure the effect of cortisol on immune system functioning.
Having a picture of the health of the HPA axis, says Monsonego, has great potential for helping physicians determine appropriate doses of steroid – a synthetic cortisol generally prescribed to people with autoimmune diseases.
When steroids are taken too long or in too high a dose, they have the same immune-damaging effect as natural cortisol released constantly into the bloodstream from the adrenal glands.
“It is well-known that patients respond differently to treatment with steroids, and we like to limit steroids as much as possible, but at some point they do not work. Patients develop resistance and you don’t know this if you can’t measure,” says Monsonego. “It would better to know beforehand if the patient is resistant than finding out during treatment.”
A blood test for cortisol effects would also be a good preventative tool, Monsonego adds.
“If someone is in danger of any type of chronic stress, we may not know when they’re at a point of [immune system] damage, and this can help people pay attention to it and reduce stress before they get sick. It’s always best to prevent disease from happening. And stress, we believe, is a major cause of many diseases.”
Monsenego points out that not everyone reacts to stress in the same way, which is why a test is important. “It may be that a certain lifestyle is not stressful to one person but it can be very stressful to someone else.”
Chronic disease itself causes psychological stress, and Monsonego believes it is possible to find a way to slow disease progression by managing the stress rather than using higher doses of pharmaceuticals.
“It’s one of the key approaches to treating these diseases: Instead of taking more and more drugs, try to take care of your lifestyle,” he advises. “Exercise, proper nutrition and stress management do a lot for your health.”