The causal relationship between stress and asthma

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between stress and asthma morbidity is longstanding, evidence of its existence is fairly recent. Improvements in our understanding of both stress system activity and asthma pathophysiology have pointed to this association as a complex neuroendocrine-immune system interaction1. The stress and immune systems play a crucial role in maintaining homeostasis. The stress response is coordinated and mediated by the centres of the stress system in the brain, along with their respective peripheral limbs. Activation of the central stress system leads to the secretion of corticotropin-releasing hormone (CRH), and hence to the stimulation of pituitary adrenocorticotropic hormone (ACTH) and adrenocortical glucocorticoid secretion. In addition, stress system activation leads to the stimulation of the systemic sympathetic and adrenomedullary nervous systems, and thus to the peripheral secretion of norepinephrine (NE), epinephrine (E), and several neuropeptides2. The immune system is responsible for the defence against different injurious agents. Once the magnitude of the immune response exceeds a certain threshold, activation of the stress response occurs, and its effects antagonise or potentiate those of the immune response. Whether stress activates or inhibits these immune responses is often dependent on the duration and quality of the stress stimulus3. The principal peripheral stress hormones, glucocorticoids and catecholamines (NE, E), affect major immune functions. Recent evidence indicates that stress hormones influence the immune response in a multi-dimensional manner; both glucocorticoids and catecholamines systemically mediate the shift towards a T helper-2 (Th2) response by suppressing antigen presentation and Th1 production and by upregulating Th2 cytokine production. On the other hand, in certain local responses and under certain conditions, stress hormones may actually facilitate inflammation via redeployment of immune cells, induction of TNFIL-1, IL-6, IL-8, and C-reactive protein production or through activation of the CRH-substance P-histamine axis. Therefore, it is becoming increasingly clear that stress hormone-induced inhibition or upregulation of the systemic or local proand anti-inflammatory mediator production as well as Th1/Th2 balance may affect disease susceptibility and outcome2,4. Data from animal models clearly indicate that stress may produce a marked increase in allergen-induced airway inflammation5. It appears that different mechanisms in acute versus chronic stress influence the inflammatory responses of the airway. In acute stress, activation of the hypothalamic-pituitary-adrenal (HPA) axis and consequent cortisol release lead to reduction of airway inflammation. Conversely, after repeated exposure to stress (chronic stress) HPA axis activity is suppressed and its anti-inflammatory effect is reduced, allowing exacerbation of the chronic airway inflammatory responses6. Clinical data indicate that exposure to stress in early development results in functional changes in im-