Here’s Why Stress Might Make You Sick

New research on mice suggests stress triggers a type of white blood cell called a mast cell, which increases histamine levels in the body.

Jutta Kuss via Getty Images

Stress. It’s a feeling that you’re likely familiar with. But how stress affects the body, from a “fight-or-flight” response during uncomfortable or threatening situations to its contribution to chronic disease like obesity remain a subject of scientific inquiry.

In a recent study published in the Journal of Leukocyte Biology, scientists using mice models set out to learn more about how stress affects the body’s immune system.

“We know that stress is a major risk factor in a number of diseases and it’s also known that some of the key symptoms that are brought on by stress involve changes in the immune system,” said Adam Moeser, lead author of the study and associate professor at Michigan State University.

While experiencing a small amount of stress has its evolutionary advantages (coaxing our prehistoric ancestors to flee predators, for example), maintaining a consistent level of stress can seriously impact your health. Chronic stress can contribute to heart disease, high blood pressure, and weakened immune response. Coping mechanisms, like drinking, smoking, and taking drugs, can exacerbate poor health.

The researchers focused on a type of white blood cell called mast cells, one of the first cells in the immune system activated when you become stressed. Located in a variety of places in the body including the gut and airways, the cells release a slew of chemicals, including histamine, when they encounter stress or foreign materials. This release of histamine can lead to sneezing or itching, and in extreme situations irritable bowel syndrome and anaphylaxis, a severe allergic reaction. (Common medicine to treat these symptoms is aptly named antihistamine.) Although scientists are aware of this connection between stress and mast cells, they still don’t know exactly how it works.

“The big question is how [mast cells] are activated and how they switch to a protective response to a maladaptive response,” said Moeser.

Adam Moeser, an endowed chair and associate professor in the college of veterinary medicine at Michigan State University, specializes in stress-induced diseases. | Michigan State University

The scientists first located a receptor called corticotropin-releasing factor receptor subtype 1 (CRF1) and discovered that it was expressed on the mast cell. Looking at CRF1, they then designed the experiment to test if this receptor was responsible for the mast cell response to stress.

“This receptor is playing a role in many diseases that have to do with the mast cell,” said Moeser. When someone is prone to allergic responses, he said, stress can exacerbate and even trigger an allergic flare.

For the experiment — which was repeated multiple times — researchers took between eight and 12 mice and divided them into two groups. The mice were genetically bred to be void of mast cells, which allowed the researchers to inject one group of mice with mast cells while the other went without. The scientists then stressed the two groups of mice: For psychological tests, they placed them in plastic tubes for a short period of time. For immune tests, they exposed them to an allergen the mice were previously sensitized to.

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The researchers then took a variety of measurements to calculate each mouse’s stress level, including their histamine levels, temperature, and whether they had a leaky gut, a common sign of stress in animals. They also looked at the behavior of each mouse, with face scratching, reduced motion, and puffy features each receiving a clinical score — the higher the score, the higher level of disease.

Mice that had CRF1 had 12-times more histamine in immune testing when compared to non-CRF1 mice. Mice without CRF1 had 54 percent less disease than those with CRF1 in immune testing and 63 percent less disease in psychological tests.

The study was funded by the National Institutes of Health.

While the researchers were expecting CRF1-deficient mice to have a reduction of disease when compared to mice with CRF1, they were surprised by the results.

“What was surprising was the magnitude of the difference,” said Moeser. “We were not expecting such a profound impact of the disease. It tells us that this is a really important target that is mediating the majority of the responses.”

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Moving forward, the researchers will continue working with human and animal cells to study the interaction between stress and mast cells. Results could help scientists develop drugs to interact with CRF1 and perhaps downplay the physical effects of stress.

Until then, the American Psychological Association has a list of recommendations to help cope with chronic stress. The group recommends scaling back on your list of projects and commitments, reaching out to family and friends for support, evaluating your sleep patterns and setting realistic expectations. Connecting with a psychologist that is trained to help manage stress can also help, the group says.

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