Researchers Identify Link Between Stress and Worsening Allergic Skin Inflammation

New Delhi: A study led by Dr Hitoshi Urakami from the Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences

has identified a connection between psychological stress and the exacerbation of allergic skin inflammation.

Researchers have demonstrated that stress impairs the ability of macrophages to clear dead cells from affected areas, worsening disease symptoms.

The research reveals how stress-activated sympathetic nerves and β2-adrenergic receptors (Adrb2) on immune cells disrupt the anti-inflammatory functions of macrophages, increasing allergic reactions.

Key findings include the discovery that stress impairs the dead cell-clearing capacity of PD-L2-positive macrophages, leading to an accumulation of dead cells in inflamed skin lesions and heightened inflammation.

Norepinephrine, released by stress-activated nerves, interacts with Adrb2 on monocytes/macrophages, altering their function. This disruption causes the failure of macrophages to effectively perform efferocytosis, a process essential for clearing dead cells and maintaining immune balance.

As a result, dead cells accumulate at the site of allergic lesions, triggering an inflammatory response and exacerbating the allergic condition.

The study further reveals that the accumulation of dead cells at the lesion site induces the expression of an eosinophil-recruiting protein, CCL24, which worsens skin allergies. Notably, the expression of CCL24 is dependent on the activity of caspase-1, an enzyme involved in inflammation.

The researchers demonstrated that inhibiting caspase-1 reduces ear swelling and reverses eosinophil infiltration in a mouse model of IgE-mediated allergic inflammation.

These findings suggest that targeting caspase-1 and CCL24 may offer promising therapeutic strategies for mitigating stress-induced allergic reactions.

Dr. Soichiro Yoshikawa, one of the lead researchers, emphasized the significance of the findings:"Our research reveals a novel mechanism where stress-induced norepinephrine worsens allergic inflammation by impairing the function of anti-inflammatory macrophages. This opens doors to targeted treatments for stress-aggravated allergic conditions."

Dr. Shin Morizane highlighted the therapeutic potential:"Inhibitors targeting Caspase-1 or CCL24 may provide effective interventions, helping patients manage stress-exacerbated allergies more efficiently."

The study, published in the Journal of Allergy and Clinical Immunology, underscores the importance of addressing psychological stress as a factor in managing allergic diseases.

Future research could lead to therapies aimed at restoring the anti-inflammatory functions of macrophages or blocking the adverse effects of norepinephrine on immune cells, offering new avenues for treating stress-induced allergic conditions.