Study reveals stress worsens skin allergies by disrupting immune functions, highlighting potential treatments using caspase-1 inhibitors to alleviate symptoms.

Stress is a feeling of emotional or physical tension. It is a natural human response to any difficulty or danger faced in our lives. Psychological stress can worsen skin allergies by interfering with the body’s inflammatory responses.

Stress Linked to Skin Allergies

Research published in The Journal of Allergy and Clinical Immunology conducted a study in a mouse model of immunoglobulin E (IgE)-mediated cutaneous allergic inflammation (IgE-CAI) has found that stress disrupts the immune system worsening the skin allergic symptoms (1^✔ ✔Trusted Source
Stress-experienced monocytes/macrophages lose anti-inflammatory function via ß₂-adrenergic receptor in skin allergic inflammation

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IgE-CAI causes swelling and increases the levels of eosinophils at the site of infection. Anti-inflammatory programmed death ligand 2 (PD-L2)-positive macrophages are specialized cells that clear the dead cells at the allergy site. This process is known as efferocytosis.

Stress reduces the ability of these specialized cells worsening the skin allergy symptoms. This is the first study to emphasize that stress disrupts macrophage function through the sympathetic nervous system.

The mouse model was injected with IgE-CAI which caused persistent ear inflammation. The neural tissue involved in IgE-CAI was first identified and then the immune cells and factors contributing to the condition were studied.

Stress Memory: How It Worsens Skin Allergies

Stress affects the function of PD-L2-positive macrophages by disrupting the activity of the β2-adrenergic receptor (Adrb2). Macrophages that develop after the disruption of Adrb2 showed reduced ability of efferocytosis.

Psychological stress decreased the gene expression in macrophages and accumulation of dead cells increased eosinophil levels at the site of infection. All these modifications led to worsened skin allergies.

The findings suggest that stress on immune cells has a long-lasting effect on macrophages that differentiate later. Severe stress on immune cells influences their function and increases the disease condition. This is called ‘Stress Memory’.

Caspase-1 Based Skin Allergy Treatment

The study further revealed that the accumulation of dead cells at the site of infection induced the expression of an eosinophil-recruiting protein, CCL24, contributing to the worsening of skin allergies. However, this expression was found to be dependent on caspase-1 enzyme activity.

Administering caspase-1 inhibitor reduces ear swelling and reverses eosinophil infiltration caused by IgE-CAI at the site of infection. The findings suggest that caspase-1 inhibitors and agents targeting CCL24 gene expression may be promising approaches for reducing skin allergies.

While avoiding stress is the ideal solution to prevent immune cell dysfunction, understanding the molecular mechanisms behind stress memory could pave the way for therapeutic strategies to reverse these effects.

Reference:

1. Stress-experienced monocytes/macrophages lose anti-inflammatory function via β2-adrenergic receptor in skin allergic inflammation – (https://www.jacionline.org/article/S0091-6749(24)01231-4/fulltext)

Source-Medindia