Stress, immune regulation, and immunity: Applications for asthma

The neuroendocrine mediators reach th cells of the immune system either thr ough the peripheral circulation or through direct innervation of lymphoid o rgans. Primary and secondary lymphoid organs are innervated by sympathetic nerve fibers. Lymphocytes and monocytes express receptors for several stres s hormones, including CRH, ACTH, cortisol, norepinephrine,and epinephrine. Therefore, it is reasonable to conclude that the neuroendocrine hormones re leased during a stressful event could alter immune function and subsequentl y alter the course of immune-based diseases. The impact of psychological st ress on immune function has been the subject of extensive research efforts. Using a variety of models from largely healthy humans undergoing various f orms of natural and experimental stress models, stress has been associated with suppression of NK activity, mitogen- and antigen-induced lymphocyte pr oliferation and in vitro production of IL-2 and IFN-gamma. Psychological st ress is also associated wit a higher rate of in vivo hypoergy to common rec all-delayed type hypersensitivity antigens. These studies have suggested th at psychological stress suppresses various components of CMI responses. Als o, data suggest that chronic stress does not simply suppress the immune sys tem, but indues a shift in the type-1/type-2 cytokine balance toward a pred ominant type-2 cytokine response. Such a change would favor the inflammator y milieu characteristic of asthma and allergic diseases. Recent studies usi ng well-controlled teenage asthmatic subjects demonstrated immunological ch anges (decreased NK cell cytotoxicity and cytokine alterations) in response to exam stress. These immun alterations are consistent with a cytokine mil ieu that could potentially worsen asthma. However, there were no changes in peak flow rates, self-report asthma symptoms, or mediation use. The lack o f correlation between stress and asthma symptoms may have been related to t he timing of the visits in relation to the stressor, the duration of the st ressor, disease severity, or a lack of accurate self-report data. Alternati vely, stress-mediated exacerbations of asthma may require multiple alterati ons by stress, including cytokine dysregulation or vagal-mediated airway hy perresponsiveness. The rationale for stress management in asthma is based u pon the notion that stress causes a change in immune balance that would fav or asthma activity in susceptible individuals. This immune imbalance can be found in TH1/TH2 cytokine changes that occur with stress. Although it has not yet been demonstrated that stress can cause or directly influence the d evelopment of asthma, it is interesting to note that both the incidence and prevalence of asthma continue to increase and are higher in urban than ina rural areas. Among other differences is the well-appreciated higher chroni c stress levels associated with urban living.