[Bronchial asthma and psychological stress]

Abstract

Bronchial asthma is a chronic airway inflammatory disease characterized by the accumulation and activation of inflammatory cells, such as eosinophils and mast cells, in the bronchial wall and airway lumen. The behavior of inflammatory cells in asthmatic airways is tightly regulated by a network of Th2 cytokines, such as IL-4, IL-5, and IL-13. Studies on asthmatics and asthma models of mice have revealed that psychological stress increases the frequency and severity of asthmatics' symptoms by enhancing the airway inflammatory responses associated with further skewing of the balance toward a Th2-dominant cytokine profile. However, the precise mechanisms linking the input to the brain (psychological stress) to the output in the airways (asthma exacerbations) are not well understood. The binding of opioid peptides to their receptors, consisting of three subtypes, mu, delta, and kappa, plays a critical role in eliciting homeostatic responses to psychological stress. The hypothalamic-pituitary-adrenal (HPA) axis is activated by opioids under stressful conditions through binding to mu-opioid receptors (MOR). Activation of the HPA axis results in the enhanced secretion of cortisol. This stress hormone has been reported to shift the immune response from Th1 to Th2 by the down-regulation of Th1 cytokine expression. Recently, we found, using a murine model, that restraint causing psychological stress exacerbates allergen-induced airway inflammation and Th2 cytokine expression via MOR in the central nervous system. A novel strategy for the management and prevention of stress-induced asthma should be developed, focusing on molecular events such as the activation of MOR.