Impact of psychosocial stress on airway inflammation and its mechanism in a murine model of allergic asthma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It has already been recognized that psychosocial stress evokes asthma exacerbation; however, the mechanism of how stress gets inside the body is not clear. This study aimed to observe the impact of psychosocial stress on airway inflammation and its mechanism in the ovalbumin-induced asthmatic mice combined with social disruption stress.</p><p><b>METHODS</b>Thirty-six male BALB/c mice were randomly divided into: control group, asthma group (ovalbumin-induced), asthma plus social disruption stress group (SDR), and SDR group. The open field video tracking system was used to assess animal behaviors. The invasive pulmonary resistance (RL) and dynamic lung compliance (cdyn) test system from Buxco was applied to detect pulmonary function. The enzyme-linked immunosorbent assay (ELISA) was utilized to determine OVA-IgE, T-helper type 2 (Th2) cytokines (IL-4, IL-5, IL-13) and corticosterone in mouse serum, the Th2 cytokines (IL-4, IL-5, IL-13, IL-6, TNF-α) in bronchoalveolar lavage fluid (BALF), and IL-6 and TNF-α levels in the supernatant of splenocytes cultured in vitro. Hematoxylin-eosin (H&E) staining was used to assess airway inflammation in lung histology. The cell count kit-8 assay (CCK-8) was applied to evaluate the inhibitory effect of corticosterone on splenocyte proliferation induced by lipopolysaccharide (LPS). Real time-PCR and Western blotting were utilized to determine glucocorticoid receptor (GR) mRNA and GR protein expression in lungs.</p><p><b>RESULTS</b>The open field test showed that combined allergen exposure and repeated stress significantly shortened the time the mice spent in the center of the open field (P < 0.01), increased ambulatory activity (P < 0.01) and the count of fecal boli (P < 0.01), but deceased vertical activity (P < 0.01). Results from pulmonary function demonstrated that airway hyperresponsiveness (AHR) was enhanced by psychosocial stress compared with allergy exposure alone. The ELISA results showed that cytokines in serum and BALF were significantly increased (P < 0.05). Moreover, the lung histology showed that infiltrated inflammatory cells were significantly increased in the asthma-SDR group compared with the asthma group (P < 0.05). Interestingly, serum corticosterone was remarkably raised by psychosocial stress (P < 0.05). In addition, the inhibitory effect of corticosterone on IL-6 and TNF-α in LPS-stimulated splenocyte cultures in vitro was diminished in the asthma-SDR group compared to the asthma group. The CCK-8 test revealed that the inhibition effect of corticosterone on splenocyte proliferation induced by LPS was significantly impaired in the SDR and asthma-SDR groups, while no significant effect was observed in the control and asthma groups. Furthermore, expression of GR mRNA and GR protein were significantly reduced in the lung tissues of the asthma-SDR group (P < 0.05).</p><p><b>CONCLUSIONS</b>Social disruption stress can promote anxiety behavior, activate the hypothalamic-pituitary-adrenal (HPA) axis, increase AHR and inflammation, and also impair glucocorticoid sensitivity and its function in a murine model of asthma. The down-regulation of GR expression induced by social disruption stress is in part associated with glucocorticoid insensitivity, which leads to asthma exacerbation.</p>

Study on the correlation between the inflammatory factors in the serum and the induced sputum and the hypothalamic-pituitary-adrenal axis function in advanced lung adenocarcinoma of different syndromes / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the correlation between the inflammatory factors in the serum and the induced sputum and the hypothalamic-pituitary-adrenal (HPA) axis function in advanced lung adenocarcinoma patients of different syndromes.</p><p><b>METHODS</b>Totally 71 patients with advanced lung adenocarcinoma were assigned to three groups according to syndrome differentiation, i.e., Shen-yang deficiency (SYD) group (28 cases), Fei-qi deficiency (FQD) group (23 cases), and yin deficiency fire excess (YDFE) group (20 cases). Another 41 healthy subjects were enrolled as the normal control group. Sputum was induced and blood samples were collected for measurement of cytokines including tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), interleukin-6 (IL-6), and interferon gamma (INF-gamma). The cytokine assay was performed using Bio-Plex Pro multi assay technology. 24-h collection of urine was performed and salivary samples of the diurnal rhythm profiles [including urinary free cortisol (UFC), urinary 17-hydroxycorticosteroids (17-OH), urinary 17-ketosteroid (17-KS), and cortisol in the serum and saliva] were obtained for assessment of the HPA axis activity.</p><p><b>RESULTS</b>A higher level of serum IL-6 and a lower level of 24-h UFC and 17-OH were found in the SYD group (P < 0.05). The urinary 17-KS was obviously lower in the SYD group than in the normal control group and the YDEE group (P < 0.05). Compared with the FQD group and the normal control group, a higher serum level of TNF-alpha and a lower level of IFN-gamma were found in the SYD group and the YDFE group (P < 0.05). The TNF-alpha and TGF-beta levels in the induced sputum obviously increased in the SYD group (P < 0.05). The IFN-gamma level in the induced sputum obviously decreased in the YDFE group (P < 0.05). The serum and salivary cortisol obviously decreased from 8: 00 am to 8:00 am the next morning in the SYD group (P < 0.05). The serum cortisol level was negatively correlated with serum TNF-alpha (r = -0.26, P = 0.03) and serum IL-6 (r = -0.25, P = 0.03). The salivary cortisol level was negatively correlated with IL-6 in the induced sputum (r = -0.29, P = 0.02). The serum IFN-gamma was positively correlated with urinary 17-OH (r = 0.21, P = 0.03).</p><p><b>CONCLUSIONS</b>The inflammatory factors of advanced lung adenocarcinoma patients of SYD syndrome were up-regulated, with the most obvious decreased or disarranged HPA axis functions. The levels of IL-6, TNF-alpha, and IFN-gamma were closely correlated with the HPA axis functions. The transformation from qi deficiency, yin deficiency to Shen-yang deficiency existed in lung adenocarcinoma patients. The levels of IL-6, TNF-alpha, and IFN-gamma in the serum and the induced sputum, as well as the HPA axis functions are important indices for microscopic syndrome typing of lung adenocarcinoma.</p>

Biomarkers and inflammatory characteristics for microcosmic syndrome differentiation of cold-phlegm syndrome and heat-phlegm syndrome in patients with bronchial asthma / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the biomarkers and inflammatory characteristics for microcosmic syndrome differentiation of cold-phlegm syndrome (CPS) and heat-phlegm syndrome (HPS) in patients with bronchial asthma.</p><p><b>METHODS</b>Patients with bronchial asthma of chronic persistent condition were distributed into three groups according syndrome differentiation, the CPS group (27 patients), the HPS group (32 patients) and the non-cold/heat-phlegm syndrome group (NP group, 31 patients), besides, a control group was setup with 33 healthy persons. Percentages of neutrophils and eosinophils (NEU, EOS) in sputum sample (collected by induction) and peripheral blood were counted; and levels of interleukin-8, -5, and -4 (IL-8, IL-5 and IL-4), interferon-gamma (IFN-gamma), leukotriene B4 (LT-B4), eosinophil cationic protein (ECP), and C-reactive protein (CRP) in sputum supernatant and serum were determined by enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>Percentage of NEU in sputum of HPS group was higher than that in the other three groups (P < 0.05); while percentages of EOS in serum and sputum of CPS group were higher than that in the other three groups (all P < 0.01). Level of ECP (a parameter closely associated with EOS) also was high in the CPS group, but IL-8 (a parameter closely associated with NEU) showed no significant difference in various groups (P > 0.05). Moreover, the CPS group showed a higher serum IL-4 (P < 0.05) but a lower IFN-gamma/IL-4 level as compared with those in the NP group (P < 0.01).</p><p><b>CONCLUSION</b>Phlegm, which is considered by Chinese medicine as an inveterate root of asthma, might be closely related with the inflammation in modern medicine. The inflammatory characteristics of asthma in patients with CPS partially present as increase of EOS, possibly show Th2 dominant trend, similar to that presented in eosinophilic asthma. Asthma with HPS embodies increase of NEU in respiratory tract. EOS and ECP might be the important markers for microcosmic syndrome differentiation of CPS, and NEU might be that for HPS.</p>