| Objective Using ovalbumin (OVA) for sensitization and airway challenge and restraint as stressor, this study established asthma and psychological stress models and aimed to (1) study the efficacy of psychological stress on central and peripheral immune functions; (2) compare the impacts of stress at different ages on airway inflammation and immune functions; (3) explore underlying mechanism of the effects of adult and early-life stress on asthma and the role of the HPA axis in this process.Methods Thirty-two healthy male weaned Wistar rat pups (21 days old) were randomly assigned to 4 groups (the asthma group, the adulthood-stressed asthma group, the childhood-stressed asthma group and the control group) of 8 each. An animal model of asthma rats exposed to psychological stress was established. Behavioral change and histological evaluation was observed. Lung tissue sections were stained with hematoxylin and eosin (HE) and leukocytes and differentiation were determined. Serum IL-4, corticosterone, immunoglobulin E (IgE) in bronchoalveolar lavage fluid (BALF) and IL-1βin brain were tested by radioimmunoassay.Results 1. After 7-day's consecutive challenge rats in the asthma group were found to be disturbed and irritable. Behavioral changes such as neezing, grasping, biting, shortness of breath and abdominal muscle contraction enhancement were observed among these animals. Some even showed bradypnoea, abnormality in rhythmic pattern of breath, mild cyanosis, paralysis, delayed or reduced action and torpid reaction. After 14-day's consecutive challenge rats exhibited weight loss, dull hair and slow response. The symptom of asthma was more severe in stressed animals. In addition, they behaved either manic or panic and compliable. 2. Morphologically, simply challenged rats showed irregular distribution of airway epithelial cells, bronchial stenosis, mucosal injury and infiltratation by eosinophils, lymphocytes and monocytes. More irregular distribution of airway epithelial cells, peribronchiolar and perivascular inflammation and severe inflammatory lesions were found in stressed rats than in the asthma group. Significant increase in the number of leukocytes and eosinophils was found in OVA-challenged groups (p< 0.01) compared with the controls. The number of eosinophils was higher in the adulthood-stressed group (p< 0.05) than the asthma group. Early-life stressed rats exhibited more leukocytes and eosinophils than the asthma group (p< 0.05).3. Serum IL-4 level was significantly accelerated by airway challenge compared with the controls (p< 0.05), and stress caused higher concentrations than simple challenge (p< 0.05). Serum corticosterone level elevation was found in all the challenged groups compared with the controls (p< 0.01), but the corticosterone concentration in childhood-stressed group was significantly lower (p< 0.05) than the control group. The adulthood-stressed group showed higher corticosterone levels than the asthma group (p< 0.05).4. No statistical difference in BALF IgE level was found among all the groups.5. Compared with control normals an increment of brain IL-1βwas observed (p < 0.05) in simply challenged and adulthood-stressed animals, but a diminution (p< 0.05) in childhood-stressed asthma rats than that of rats in the asthma group.Conclusion 1. Psychological stress induced immune disorders and asthma severity in rats. Stress elevated peribronchiolar and pulmonary inflammation in adult asthma rats, induced behavioral alteration, the significant higher levels of numbers of leukocytes and eosinophils and disorders of a number of immune indicators.2. Stress increased serum corticosterone and central IL-1βlevels in adulthood-stressed rats but decreased the concentration of these indicators in childhood-stressed animals.3. The relationship between stress and asthma pathophysiology points to an alteration of the neuroendocrine-immune system interaction and the HPA axis may play a major role in this process. But the underlying mechanism of the effects of childhood-stress is different from that of adulthood-stress. Adulthood stress induced HPA axis hyperactivity, while early-life stress exerts a long-lasting suppressive effect on HPA axis responsiveness. The age of psychological stress exposure may significantly affect the nature and direction of the impacts on asthma, inducing opposite effects. |
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