Assistant Professor Northeastern Univ., United States
Introduction/Rationale: Recent research has revealed important interactions between the neuroendocrine system and the immune system, but the precise mechanisms of this relationship remain unclear. Stress is known to trigger inflammation throughout the body, suggesting that stress hormones such as glucocorticoids and catecholamines may influence the activity of innate immune cells, including neutrophils. This study explores how stress hormones and neutrophils interact and contribute to behavioral changes.
Methods: Using a mouse model of chronic restraint stress and measured levels of neutrophil extracellular traps (NETs) in plasma and tissues. We also exposed human neutrophils ex vivo to the stress hormones cortisol and epinephrine to assess their effect on NET formation. Additionally, we analyzed changes in receptor expression and hormone production by neutrophils, and tested the behavioral effects of NET components in mice. Finally, we examined gene expression changes in NET proteins following glucocorticoid receptor activation in human cells.
Results: Chronic restraint stress in mice resulted in elevated plasma NETs and increased NET formation. In human neutrophils, both cortisol and epinephrine stimulated NET production ex vivo. NET formation was associated with higher expression of adrenergic and glucocorticoid receptors on neutrophils, as well as increased neutrophil production of cortisol and epinephrine, indicating a possible autocrine or paracrine feedback loop. Administration of NET components to mice induced anxiety-like behaviors, and activation of the glucocorticoid receptor in human cells led to increased expression of NET-related genes.
Conclusion: Our data shows that stress hormones can drive neutrophil inflammatory responses and that neutrophil-derived inflammation may contribute to behavioral changes following stress. This work highlights the role of inflammation in mediating the effects of stress on mood and behavior.
