• The Journal of Internal Korean Medicine
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• v.21 no.1
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• pp.31-38
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• 2000

Background : Nowadays asthma is considered to be the inflammatory disease characterized by airway hyperresponsiveness and pulmonary eosinophilia, and mediated by Th lymphocytes expressing the Th2 cytokine pattern. In many recent studies, molecular biological methods have been used to investigate the role of cytokines in pathogenesis and new therapeutic targets of asthma. Objective : We aimed to identify the effect of Armeniacae Arnarum Semen and Platycodi Radix on the transcriptional activities of cytokine IL-4, IL-5 and IL-6 involved in asthma model. Materials and Methods : RBL-2H3 cell lines were used. Cells were stimulated with calcium inophore for maximal gene expression. After 24 hours of Armeniacae Arnarum Semen and Platycodi Radix-treatment, total cellular RNAs were collected using Trizol solution method. Then transcriptional activities of IL-4, IL-S and IL-6 were measured by RT-PCR with electrophoresis. Results : In IL-4 study, Armeniacae Arnarum Semen treated group showed 48.4% of transcriptional activities compared to the control group and Platycodi Radix treated group showed 45.4% of transcriptional activities compared to the control group. In IL-5 study, Armeniacae Arnarum Semen treated group showed 52.7%of transcriptional activities compared to the control group and Platycodi Radix treated group showed 60.2% of transcriptional activities compared to the control group. In IL-6 study, Armeniacae Amarum Semen treated group showed 42.3% of transcriptional activities compared to the control group and Platycodi Radix treated group showed 69.1% of transcriptional activities compared to the control group. Conclusion : This study shows that Armeniacae Arnarum Semen and Platycodi Radix have the inhibitory effect on the transcription of IL-4, IL-5 and IL-6 gene expression in RBL-2H3 cell lines. Advanced studies are required to investigate the mechanisms of inhibition by herbal medicine in asthma model.

• The Journal of Internal Korean Medicine
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• v.27 no.2
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• pp.394-406
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• 2006

Backgrounds and Objectives: Asthma is considered to be an inflammatory disease characterized by airway hyperresponsiveness and Pulmonary eosinophilia. And it is known the structure and function of IL-5, its receptor and the mechnism IL-5 triggered eosinophil accumulation and inflammaion of the airways. At this point of view, we assume which oriental materia medics can the splenocyte inhibit from secreting the IL-S in vitro. Material and Methosds: We used the splenocyte of mouse 8 weeks after its birth, and then cnltivated those into the 2 experimental groups and control group for 48 hours. The culture medium of experimental groups were made of $1{\mu}g/ml,\;10{\mu}g/ml$, oriental materia medics, representative. And the culture media of control group was given no oriental materia medica. Then, we assayed the quantity of cytokine-expression by the Sandwich ELISA. The quantifies of cytokine-expression of the experimental groups were compared with that of the control group which was standardized These method were used for the all of oriental materia medica treated. Results: In this study, we demonstrated that 12 oriental materia medica that inhibit the splenocyte from secreting the IL-5 in both $1{\mu}g/ml,\;and\;10{\mu}g/ml$ culture media. Those were Equiseti Herbs, Sophorae Subprostratae Radix, Moutan Radicis Cortex. Trichosanthis Radix, Buddleiae Flos. Cyperi Rhizoma. Benincasae Semen, Armeniacae Semen. Zedoariae Rhizoma, Astragali Semen, Dolichoris Semen. Lilii Bulbus, Asparagi Radix, Atractylodes Rhizoma White, Polygonati Officinallis Rhizoma. Conculusions: These findinga indicate that some oriental materia medica, specially Antipyretics, Herbs for Resolving Phlegm, Relieving Cough and Calming Wheezing and Herbs for Tonifring and Invigorating effects inhibit the splenocyte from secreting the IL-5. And further study experimented in vivo is needed for treating IL-5-driven inflammatory disease including asthma.

• Tuberculosis and Respiratory Diseases
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• v.63 no.2
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• pp.145-153
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• 2007

Background: Asthma is a syndrome that is characterized by a variable degree of airflow obstruction, bronchial hyperresponsiveness, and airway inflammation. Colchicine is an inexpensive and safe medication with unique anti-inflammatory properties. IL-1Ra (Interleukin-1 receptor antagonist) mediates the anti-inflammatory effect in human inflammatory diseases, including asthma. This study examined whether IL-1Ra mediates the anti-inflammatory effect of colchicine in normal human bronchial epithelial cells (NHBE), RAW 264.7 cells (murine macrophage cell line), and a mouse lung. Methods: NHBE, RAW 264.7 cells and BALB/c mice were stimulated with colchicine, and the increase in the IL-1Ra level was estimated by ELISA, Western analysis and RT-PCR analysis. Results: Colchicine stimulated NHBE and RAW 264.7 cells to release IL-1Ra into the supernatant in a dose-and time-dependent manner. The major isoform of IL-1Ra in NHBE and RAW 264.7 cells is type I icIL-1Ra, and sIL-1Ra, respectively. IL-1Ra up-regulation was blocked by PD98059, a specific inhibitor in MAPK pathways. Colchicine also stimulated the secretion of IL-1Ra into the bronchoalveolar lavage (BAL) fluid of BALB/c mouse. Conclusion: Colchicine stimulates an increase in the IL-1Ra level both in vivo and in vitro, and might have an anti-inflammatory effect.

• Journal of Life Science
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• v.16 no.5
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• pp.780-787
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• 2006

Asthma is a chronic inflammatory disorder of the airways, which characterized by bronchial hyperresponsiveness, reversible airflow limitation and respiratory symptoms. Internationally, the prevalence of asthma has been increased over last 3 decades. Recently, several studies of asthma have been reported with gradually increasing importance. To tesify the hypothesis that interleukin (IL)-4 and IL-10 may be an important determinant of the severity of airway inflammation, their expression was studied in mouse model of asthma. BALB/c mouse, IL-4 Knockout (KO) mouse and IL-10 KO mouse were sensitized with intraperitoneal injection of ovalbumin adsorbed to aluminum potassium sulfate, followed by challenges with intranasal ovalbumin on 3 consecutive days. The severity of pulmonary inflammation was assessed by eosinophilia in BAL fluid, number of total BAL cells, histopathological changes in lung tissues, and immunohistochemical staining against IL-4 and IL-10. In BAL fluid, the number of total cells was significantly increased in asthma induced mouse compare to the control. In asthma induced mouse, eosinophil was increased to 56% and neutrophil was 0.2%. In H &E stains, eosinophilic infiltration and epithelium hyperplasia were clearly noticed in asthma induced mouse. In immunohistochemical staining for IL-4 and IL-10, there was no positive reaction in control group. However, very strong reactions were appeared in asthma induced group. In this research, IL-4 and IL-10, which seem to play a central role in allergic asthma, KO mouse was utilized to test the causative relationship between airway inflammation and role of specific cytokine. Asthma induced IL-4 and IL-10 KO mice showed much decreased inflammatory reactions in the number of total BAL cells, in eosinophilic infiltration, and in immunohistochemical stains against diverse inflammatory proteins. These results suggest that IL-4 and IL-10 increase the asthmatic reactions in vivo mice model.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.341-350
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• 1998

Background: Airway hyperreponsiveness is a cardinal feature of asthma. It consists of both an increased sensitivity of the airways, as indicated by a smaller concentration of a constrictor agonist needed to initiate the brochoconstrictor response and an increased reactivity, increments in response induced subsequent doses of constrictor, as manifested by slopes of the dose-response curve. The purpose of this study is to observe the relationship between bronchial sensitivity and reactivity in asthmatic subjects. Method: Inhalation dose-response curves using methacholine were plotted in 56 asthmatic subjects. They were divided into three groups(mild, moderate and severe) according to clinical severity of bronchial asthma. PC20 were determined from the dose-response curve as the provocative concentration of the agonist causing a 20% fall in FEVl. PC40 were presumed or determined from the dose response curve, using the PC20 and the one more dose after PC20. Reactivity was calculated from the dose-response curve regression line, connecting PC20 with PC40. Results: PC20 were 1.83mg/ml in mild group, 0.96mg/ml in moderate, and 0.34mg/ml in severe. PC40 were 7.l7mg/ml in mild group, 2.34mg/ml in moderate, and 0.75mg/ml in severe. Reactivity were $24.7{\pm}17.06$ in mild group, $46.1{\pm}22.l0$ in moderate, and $59.0{\pm}5.82$ in severe. There was significant negative correlation between PC20 and reactivity (r= -0.70, P<0.01). Conclusion: Accordingly, there was significant negative correlation between bronchial sensitivity and brochial reactivity in asthmatic subjects. However, in some cases, there were wide variations in terms of the reactivity among the subjects who have similar sensitivity. So both should be assessed when the bronchial response tor bronchoconstrictor agonists is measured.

• Tuberculosis and Respiratory Diseases
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• v.46 no.2
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• pp.175-184
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• 1999

Background: Bronchial asthma is characterized by chronic eosinophilic inflammatory airway disease associated with bronchial hyperresponsiveness and reversible airway obstruction. Bronchial inflammation in asthma may depend in part on the activation of T helper lymphocytes that elaborate proinflammatory cytokines. T helper (Th) lymphocytes can be divided into two categories; Th1 lymphocytes, which secrete IL-2, IL-12 and IFN-$\gamma$, and Th2 lymphocytes, which secrete IL-4, IL-5, IL-6 and IL-10. Th2 lymphocytes appear to induce allergic responses, whereas Th1 lymphocytes induce delayed-type hypersensitivity response. Some infections, such as tuberculosis, cultivate a Th1 immunological environment and inhibit Th2 lymphocytes function. The presence of such infections might inhibit Th2 immune responses and thus protect development of atopic diseases. Method: 15 patients with allergic bronchial asthma, 10 patients with intrinsic bronchial asthma, and 10 healthy volunteers were studied. The serum concentrations of IFN-$\gamma$, IL-12, IL-4, IL-5, and IL-10 were measured by ELISA method and tuberculin skin test was estimated in different groups. Results: The positive response rates of tuberculin test were 46.7% in patients with allergic asthma, 100% in patients with intrinsic asthma and 60% in normal controls. The positive response rates were significantly lower in patients with allergic asthma than those of in patients with intrinsic asthma (p<0.05). Degree of responses to tuberculin test were $12.0{\pm}9.6mm$ in patients with allergic asthma, $18.4{\pm}4.5mm$ in patients with intrinsic asthma and $10.9{\pm}8.8mm$ in normal controls. The degree of responses were significantly reduced in patients with allergic asthma than those of patients with intrinsic asthma (p<0.05). The serum levels of IL-5 in patients with allergic asthma were significantly higher than in patients with intrinsic asthma and normal controls (p<0.05), although it was insignificant. the serum levels of IL-4 and IL-10 in patients with allergic asthma were higher than that of intrinsic asthma and normal controls. The serum levels of IL-12 and IFN-$\gamma$ in patients with allergic asthma and intrinsic asthma were significantly lower than those in normal controls(p<0.05). The serum levels of total immunoglobulin E (IgE) and peripheral blood eosinophile counts in patients with allergic asthma were significantly higher than those in normal controls. Peripheral blood esinophil counts had a significant correlation with the serum levels of total IgE, IL-5 and IL-10 in patients with allergic asthma (p<0.05). Conclusion: These results have showed that Th1 lymphocyte functions were lowered and Th2 lymphocyte functions were elevated in patients with allergic asthma than those in normal controls. Suppression of Th1 lymphocyte functions by activation of Th2 lymphocyte might be one of the important aspects of pathogenesis in allergic bronchial asthma.

• Tuberculosis and Respiratory Diseases
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• v.45 no.5
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• pp.1012-1021
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• 1998

Background : It is known that airway inflammation is present in most patients with asthma, but the relationship between symptoms and the severity and nature of airway inflammation has not been established. Cough variant asthma is defined as an asthma in which the dominant symptom is cough, and the condition can be successfully treated with inhaled steroids. This study was performed to evaluate the time course of bronchial responsiveness according to an inhaled anti-inflammatory therapy and the factors which affect the resolution of bronchial responsiveness, and an efficacy of nedocromil to cough asthma. Method: A prospective study for the investigation of bronchial responsiveness according to an inhaled anti-inflammatory treatment in sixty-one cough asthmatics was performed. Twenty-three entered budesonide ($400{\mu}g{\times}2/day$), twenty-two entered nedocromil ($4mg{\times}2/day$) and sixteen patients entered combined group. The bronchial hyperresponsiveness (BHR) was estimated by methacholine challenge test using counted breath method. The symptom was estimated by 'symptom score'. Reevaluation of BHR and symptom was performed at 2 month after treatment, and if BHR was not resoluted at this time, regarded as a non-responder, and then follow-up of BHR and symptom was performed at 4- and/or 6 month after treatment. Results: The improvement of BHR and symptom was significant in 2 month (p<0.05), but there was no change of them during follow-up period of 4- and/or 6 month in non-responders. In comparison of allergic markers such as serum total IgE, peripheral eosinophil count and skin test reactivity between responders and non-responders, there was no difference in each other. However, in comparison of other factors such as cumulative pack-years, symptom duration, age, gender, and the initial degree of PC20, there was a significant difference in each other(p<0.05). The percent of patients with the resolution of BHR in 2 month was not different in each group(p=0.95). There was no significant difference in the degree of improvement of BHR and symptom in each group. Conclusion: Bronchial responsiveness and symptom was not significantly improved in non-responders during follow-up period of 4- and/or 6 month. The effect of inhaled nedocromil was equivalent to that of inhaled steroid in cough asthmatics, and the response to combined treatment is not superior to that achieved by either of these agents used alone.

• Tuberculosis and Respiratory Diseases
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• v.39 no.3
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• pp.219-227
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• 1992

Background: Acute and chronic airway inflammation are important in the pathogenesis of bronchial asthma. Corticosteroids have proved to be very effective in the management of asthma. Although the mechanism by which they produce this effect is still debated, suppression of the inflammatory response is thought to be the most likely. Although inhaled steroids are known to be safe and have less side effects than oral steroids, the extent which inhaled steroids have beneficial and the detrimental effects in the treatment of asthma has remained open to question. Budesonide is a recently developed corticosteroid for inhalation treatment with a strong local effect combined with rapid inactivation in the systemic circulation. We set out to look in more detail at the time course of change in bronchial reactivity, clinical symptoms and the effects on the adrenal function during 6 weeks of treatment with budesonide (800 ug per day). Methods: Clinical symptoms, pulmonary function test, histamine $PC_{20}$, serum ACTH and cortisol (8 AM and 4 PM) were measured in 23 allergic asthmatic patients before and after 6 weeks of treatment with budesonide. Results: 1) Pulmonary function test; PEFR, FEV1 and FVC after 6 weeks of treatment with budesonide were higher than those before treatment. 2) Clinical symptoms; Clinical symptoms were significantly improved after 3 weeks and 6 weeks of treatment with budesonide. 3) Histamine provocation; Histamine $PC_{20}$ after 6 weeks of treatment with budesonide was significantly higher than that before treatment. 4) Adrenal function; 6 weeks of budesonide therapy did not significantly affect the level of serum ACTH and cortisol. Conclusion: From these results, it is concluded that budesonide therapy improved the clinical symptoms, pulmonary function and bronchial hyperreactivity after 3 weeks of treatment and the improvement after 6 weeks of treatment was higher than that after 3 weeks of treatment. During 6 weeks of treatment with budesonide, the inhibitory effect on the adrenal function was not obvious.

• Tuberculosis and Respiratory Diseases
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• v.52 no.1
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• pp.24-36
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• 2002

Background: Bronchial reactivity is known to be a component of airway hyperresponsiveness, a cardinal feature of asthma, with bronchial sensitivity, and is increments in response to induced doses of bronchoconstrictors as manifested by the steepest slope of the dose-response curve. However, there is some controversy regarding methods of measuring bronchial reactivity and clinical impact of such measurements. The purpose of this study was to evaluate the clinical significance and assess the clinical use by analyzing the relationship of the bronchial sensitivity, the clinical severity and the changes in pulmonary function with bronchial reactivity. Method: A total of 116 subjects underwent a methacholine bronchial provocation test. They were divided into 3 groups : mild intermittent, mild persistent, moderate and cough asthma. Severe patients were excluded. Methacholine PC20 was determined from the log dose-response curve and PC40 was determined by one more dose inhalation after PC20. The steepest slope of log dose-response curve, connecting PC20 with PC40, was used to calculate the bronchial reactivity. Body plethysmography and a single breath for the DLCO were done in 43 subjects before and after methacholine test. Results: The average bronchial reactivity was 38.0 in the mild intermittent group, 49.8 in the mild persistent group, 61.0 in the moderate group, and 41.1 in the cough asthma group. There was a weak negative correlation between PC20 and bronchial reactivity. A heightened bronchial reactivity tends to produce an increased clinical severity in patients with a similar bronchial sensitivity and basal spirometric pulmonary function. There were significant correlations between the bronchial reactivity and the initial pulmonary function before the methacholine test in the order of sGaw, Raw, $FEV_1$/FVC, MMFR. There were no correlations between the bronchial sensitivity and the % change in the pulmonary function parameters after the methacholine test. However, there were significant correlations between the bronchial reactivity and the PEF, $FEV_1$, DLCO. Conclusion: There was weak significant negative correlation between the bronchial reactivity and the bronchial sensitivity, and the bronchial reactivity closely reflected the severity of the asthma. Accordingly, measuring both the bronchial sensitivity and the bronchial reactivity can be of assistance in assessing of the ongoing disease severity and in monitoring the effect of therapy.