Stress can worsen symptoms of skin allergies like eczema (Prostock-studio/Shutterstock)

Mouse model shows stress can worsen skin allergy symptoms for those with conditions like eczema

TOKYO — Ever noticed how your skin seems to flare up before a big presentation or during a stressful work week? Scientists have long suspected a link between psychological stress and worsening allergy symptoms, but the biology behind this connection has remained elusive until now. A study from Japanese researchers has uncovered the cellular chain reaction that explains why stress can make your skin allergies more severe.

In research published in the Journal of Allergy and Clinical Immunology, researchers found that when we’re stressed, certain immune cells called macrophages (which normally help reduce inflammation) essentially “forget” how to do their protective job. These cellular changes can persist for up to a week after the stressful event, potentially explaining why periods of high stress often lead to prolonged allergy symptoms.

The study focused on a specific type of allergic skin inflammation that develops when specialized antibodies called IgE encounter allergens. These IgE antibodies are like sentinel guards that trigger an allergic response when they detect potentially harmful substances. However, in allergic conditions, they overreact to harmless things like pollen or pet dander. This process mirrors what happens in conditions like atopic dermatitis (eczema). The researchers subjected laboratory mice to periodic restraint stress, similar to what humans might experience during periods of psychological stress, and then triggered an allergic skin reaction.

They found that stressed mice developed much more severe allergic reactions than their unstressed counterparts, with significantly more inflammatory cells called eosinophils accumulating in their skin. Eosinophils are white blood cells that, while normally helping fight parasitic infections, can cause tissue damage when too many accumulate during allergic reactions.

During stress, the sympathetic nervous system, our “fight or flight” response, releases a hormone called norepinephrine. This stress hormone interacts with special receptors on macrophages. When repeatedly exposed to stress-induced norepinephrine, these macrophages become less effective at their main anti-inflammatory job: cleaning up dead cells in the tissue, a process called efferocytosis.

Think of it like a neighborhood cleanup crew suddenly becoming bad at their job. When dead cells aren’t properly cleared away, they start to decompose and release danger signals that trigger more inflammation. This kicks off a vicious cycle where more inflammatory cells are recruited to the area, making the allergic reaction worse.

When researchers blocked the ability of macrophages to respond to norepinephrine, the stress-induced worsening of allergic reactions didn’t occur. What’s particularly interesting is how long these effects can last.

“Our findings suggest that the impact of psychological stress on immune cells is long-lasting and can even affect macrophages that differentiate later. This phenomenon, referred to as ‘stress memory,’ implies that severe stress leaves a lingering imprint on immune cells, influencing their function and contributing to disease development,” explains study author Soichiro Yoshikawa, Ph.D., from Juntendo University, in a statement.

There is potential for treatment, though. When stressed mice accumulated dead cells at the inflammation site, this triggered the production of CCL24, a protein that attracts more inflammatory cells. However, the researchers found they could block this process using inhibitors of an enzyme called caspase-1. When they administered these inhibitors, they observed reduced ear swelling and fewer inflammatory cells in the affected areas, suggesting a possible therapeutic approach.

“This study is the first in the world to demonstrate that stress, through the sympathetic nervous system, disrupts macrophage function, which normally helps suppress allergic reactions, thereby intensifying allergic responses,” notes Dr. Yoshikawa. “Anti-inflammatory macrophages play crucial roles in various diseases, including cancer, autoimmune disorders, and wound healing. This study not only sheds light on the impact of stress on allergic inflammation but also lays the groundwork for exploring how stress exacerbates other diseases involving these macrophages.”

Stress can derail our immune system’s ability to control allergic reactions, but this study also points to potential solutions. While researchers work on targeting these specific molecular pathways, the findings underscore that managing stress isn’t just good for mental health; it’s essential for immune system function.