THE RELATIONSHIP between psychological stress and common illnesses, including allergic conditions, has long been acknowledged in clinical practice. Stress activates the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS), leading to the release of stress hormones like glucocorticoids, epinephrine, and norepinephrine. These hormones alter immune responses, suppressing TH1 cells and natural killer cells while modulating the function of other immune cells such as neutrophils and T cells. This can increase susceptibility to illnesses, including cancer and infections.
Atopic dermatitis (AD), an allergic skin condition characterised by inflammation and heightened IgE levels, is often worsened by psychological stress. Stress is believed to amplify the sensitisation phase of AD by promoting type 2 cytokine and IgE production, though the precise mechanisms remain unclear. Research in mice has identified that psychological stress exacerbates IgE-mediated cutaneous allergic inflammation (IgE-CAI), an AD model, by impairing the clearance of dead cells by anti-inflammatory macrophages. This disruption leads to an accumulation of dead cells, releasing pro-inflammatory signals that intensify skin inflammation.
The underlying process involves norepinephrine, released under stress, which suppresses the expression of efferocytosis-related genes in macrophages. This results in reduced capacity to clear dead cells, prolonging inflammation and promoting eosinophil infiltration. Importantly, stress appears to imprint a “memory” on monocytes, altering their function even after the stress event. This phenomenon, linked to epigenetic changes, could explain the prolonged exacerbation of allergic diseases post-stress.
These findings extend to human monocytes, suggesting that stress-induced reductions in macrophage function may contribute to exacerbations in stress-related diseases like asthma. Enhancing macrophage efferocytosis could offer a therapeutic strategy to counteract the inflammation associated with stress-aggravated conditions.
In conclusion, psychological stress significantly influences immune responses and exacerbates allergic and inflammatory diseases. Future therapies targeting macrophage function and efferocytosis may provide effective solutions to manage stress-induced inflammation.
Katie Wright, EMJ
Reference
Urakami H et al. Stress-experienced monocytes/macrophages lose anti-inflammatory function via β2-adrenergic receptor in skin allergic inflammation. J Allergy Clin Immunol. 2024;DOI:10.1016/j.jaci.2024.10.038.
