Psychological Stress and Immune Response Mechanisms

Psychological stress engages a complex network of neural, endocrine and immune pathways that together determine the organism’s capacity to respond to challenge. Acute stress triggers activation of the hypothalamic–pituitary–adrenal axis and sympathetic nervous system, leading to rapid release of glucocorticoids and catecholamines. These mediators modulate immune cell trafficking, cytokine release and the balance between innate and adaptive immunity. Chronic stress, by contrast, is associated with sustained low-grade inflammation, impaired antiviral defences and altered leukocyte subset distribution. Crosstalk between brain and immune organs shapes behavioural, metabolic and cardiovascular outcomes across the life course. Understanding these mechanisms is essential to developing interventions that leverage psychological and pharmacological approaches to bolster resilience, mitigate inflammatory pathology and improve global health.

Research from Nature Portfolio

A seminal investigation assessed both plasma and salivary concentrations of key inflammatory markers during socio-cognitive stress. By measuring IL-1β, IL-18 and IL-6 before, during and after an academic‐exam paradigm, researchers demonstrated tight correlations between emotional states of anger and anxiety and dynamic cytokine shifts in both compartments. Salivary assays were validated as a non-invasive proxy for systemic inflammation, revealing that distinct immune mediators align with discrete emotional responses. This work underpins current efforts to monitor stress-induced immune changes in real-world settings and to tailor precision interventions that target specific cytokine networks.

Psychological Stress and Immune Response Mechanisms publication trend

The graph below shows the total number of articles in psychological stress and immune response mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Hypothalamic–pituitary–adrenal (HPA) axis: A neuroendocrine system that controls stress hormone release, primarily cortisol, which modulates immune function.

Glucocorticoids: Steroid hormones produced by the adrenal cortex in response to stress, exerting broad anti-inflammatory effects and influencing leukocyte distribution.

Cytokines: Small secreted proteins (e.g. IL-1β, IL-6, TNF-α) that coordinate immune cell communication and inflammatory responses.

Innate immunity: The rapid, non-specific defence system comprising neutrophils, macrophages and natural killer cells activated immediately upon stress or infection.

Salivary assays: Non-invasive techniques to measure hormones and cytokines in saliva as proxies for systemic immune and endocrine activity.

References

1. A multiscale inflammatory map: linking individual stress to societal dysfunction. Frontiers in Science (2024).
2. From mental strain to gut pain: A brain‐gut pathway transducing psychological stress to intestinal inflammation. Clinical and Translational Medicine (2023).
3. The plasmatic and salivary levels of IL-1β, IL-18 and IL-6 are associated to emotional difference during stress in young male. Scientific Reports (2018).
4. Acute stress induces an inflammation dominated by innate immunity represented by neutrophils in mice. Frontiers in Immunology (2022).