Prevalence of asthmatic symptoms and clinical characteristics in elderly asthmatic patients / 천식및알레르기

No abstract available.

The role of dependent pathway in eosinophil apoptosis / 천식및알레르기

BACKGROUND: Interleukin-5 (IL-5), IL-3, and GM-CSF are known to prolong the survival of eosinophils, and IL-5 has the most potent effect on eosinophil survivaL It is also known that divergent signals induce apoptosis in different cells. But, There have been few reports on about the intracellular signals that trigger the effectors of apoptosis. Cyclic AMP (cAMP) can modulate apoptosis in many cells. But, the role of intracellular cAMP in the IL-5 induced eosinophil survival is still not completely understood. OBJECTIVES: This study was aimed to elucidate the role of intracellular cAMP in IL-5 induced eosinophil survival. MATERIAL AND METHOD: Eosinophils were isolated from peripheral blood of atopic patients. Eosinophil viability was measured by means of propidium iodine (PI) method and the number of viable cells was counted by FAC scan (Becton Dickinson, USA). Cells were cultured with or without IL-5, and also with various cAMP-elevating agents (dibutyryl cAMP, 8-bromo-cAMP, N6- benzoyl cAMP). The concentrations of cAMP were measured by cAMP enzyme immunoassay system(BiotrakTM, Amersham). Finally cAMP dependent protein kinase A inhibitor (H8) was added to eosinophils to examine the effect of decreased intracellular cAMP activity on the viability of eosinophils stimulated with IL-5. RESULTS: The percentage of viable eosinophils was reduced rapidly from 92.1+/-1.8% to 8.23+/- 3.41% without IL-5 (p<0.05; n=ll, 4-day incubation). Upon addition of IL-5, it was increased to 33.02+7.8% (p<0.05; n=ll). In the absence of IL-5, the addition of cAMP-elevating agent increased eosinophil viability in a dose-dependent manner. Upon addition of H8 (24 uM), the eosinophil viability increased by IL-5 (52.5+/-6.4%) was significantly reduced to 27.2+/-5.4% (p<0.05;n=7). Compared with tissue culture media (TCM) only, IL-5 produced persistent elevation of intracellular cAMP of eosinophils in a time and dose dependent manner.

The Production and Correlation of Silica Induced Proinflammatory Cytokines and TGF-beta from Monocytes of Balb/C Mice / 결핵

BACKGROUND: Chronic inhalation of silica induces the lung fiborsis. The alveolar macrophages ingest the inhaled silica they liberate the pro-inflammatory cytokines such as IL-i/A IL-C, TNF-a and fibrogenic cytokines, TGF-beta and PDGF. Cytokines liberated from macrophage have pivotal role in pulmonary fibrosis. There is a complex cytokine network toward fibrosis. However, the exact roles and the interaction among the proinflammatory cytokines and TGP-beta, a fibrogenic cytokine, have not been defined, yet In this study, we investigated silica induced IL-1/beta, IL-6, TNF-alpha and TGF-beta production and the effect of IL-1/beta, IL-6, TNF-alpha on the production of TGF-beta from lung macrophages of Balb/C mice. METHOD: We extracted the lung of Balb/C mice and purified monocytes by Percoll gradient method. Macrphages were stimulated by silica (SiO2) in the various concentration for 2, 4, 8, 12, and 24 bows. The supernatants were used for the measurement of protein levels by bioassay, and cells for the levels of mRNA by in situ hybridization. RESULTS: The production of IL-6 was not observed till 4 hours, and reached the peak levels at S horns after stimulation of silica. The production of TNF-alpha increased from 2 hours and reached the peak levels at 4 hours after stimulation of silica. The spontaneous TGF-beta production reached the peak levels at 24 hours. TNF-alpha upregulated the silica induced TGF-beta production Silica induced TGF-beta production was hooked by pretreated anti-TNF-alpha antibody. In situ hybridization revealed the increased positive signals at 4 hours in IL-6, at 4 hours in TNF-alpha and 12 hours in TGP-beta. CONCLUISON: The results above suggest that silica induced the sequential production of IL-6, TNF-alpha and TGF-beta from macrophages and TNF-alpha upregultaes the production of TGF-beta from silica-induced macrophages.

Silica induced Expression of IL-1beta, IL-6, TNF-beta, TGF-alpha, in the Experimental Murine Lung Fibrosis / 결핵

BACKGROUND: Silica-induced lung diseases is characterized by the accumulation of inflammatory cells at early stage and fibrosis in pulmonary parenchyma and interstitium at late stage. As a consequence of inflammation, silicosis is accompanied with the expansion of interstitial collagen and the formation of fibrotic nodule. In this process, several kinds of lung cells produce cytokines which can amplify and modulate pulmonary fibrosis. The alveolar macrophage is a potent source of proflammatory cytokines and growth factor. But in the process of silicotic inflammation and fibrosis, there are many changes of the kinetics in cytokine network. And the sources of cytokines in each phase are not well mown. METHOD: 2.5 mg of silica was instillated into the lung of C57BL/6J mice. After intratracheal instillation of silica, the lungs were removed for imunohistsochemical stain at 1. 2,7 day, 2, 4,8, 12 week, respecilvely. We investigated the expression of IL-1beta, IL-6, TNF-alpha and TGF-beta in lung tissue. RESULTS: 1) The expression of IL-6 increased from 1 day after exposure to S weeks in vascular endothelium. Also peribronchial area were stained for IL-6 from 7 days and reached the peak level for 4 weeks. 2) The IL-1beta was expressed weakly at the alveolar and peribronchial area through 12 weeks. 3) The TNF- expressed strongly at alveolar and bronchial epithelia during early stage and maintained for 12 weeks. 4) TGF-beta was expressed strongly at bronchial epithelia and peribronchial area after 1 week and the strongest at 8 weeks. CONCLUISON: The results above suggests IL-6, TNF- appear to be a early inflammatory response in silica induced lung fibrosis and TGF-beta play a major role in the maintenance and modulation of fibrosis in lung tissue. And the regulation of TNF- production will be a key role in modultion of silica-induced fibrosis.

Lipopolysaccharide-induced Synthesis of IL-1beta, IL-6, TNF-alpha and TGF-beta by Peripheral Blood Mononuclear Cells / 결핵

BACKGROUND: Endotoxin (LPS lipopolysaccharide), a potent activator of immune system, can induce acute and chronic inflammation through the production of cytokincs by a variety of cells, such as monocytes, endothelial cells, lymphocytes, eosinophils, neutrophils and fibroblasts. LPS stimulate the mononucelar cells by two different pathway, the CD14 dependent and independent way, of which the former has been well documented, but not the latter. LPS binds to the LPS-binding protein (LBP), in serum, to make the LPS-LBP complex which interacts with 0D14 molecules on the mononuclear cell surface in peripheral blood or is transported to the Ussues. In case of high concentration of LPS, LPS can stimulate directly the macrophages without LBP. We investigated to detect, the generation of proinflammatory cytokines such as interleukin 1 (IL-1), IL-6 and TNF-alpha, and fibrogenic cytokine, TGF-beta, by peripheral blood mononuclear cells (PBMC) after LB'S stimulation under serum-free conditions, which lacks LBPs. METHODS: PBMC were obtained by centrifugation on Ficoll Hypaque solution of peripheral venous bloods from healthy normal subjects, then stimulated in the presence of LPS (0.1 microgram/mL to 100 microgram/mL). The activities of IL-1, IL-6, TNF, and TGF-betawere measured by bioassaies using cytokines - dependent proliferating or inhibiting cell lines. The cellular sources producing the cytokines was investigated by immunohistochemical stains and in situ hybridization. RESULTS: PBMC started to produce IL-6, TNF-alpha and TGF-beta in 1 hr, 4 hrs and 8hrs, respectively, after LPS stimulation The production of IL-6, TNF-alpha and TGF-beta continuously increased 96 His after stimulation of LPS. The amount of production was 19.8 ng/ml of IL-6 by 105 PEMC, 4.1 ng/mL of TNF by 106 PBMC and 344 pg/mL of TGF-betaby 2 x 106 PBMC. The immunoreactivity to IL-6, TNF-alpha and TGF-betawere detected on monocytes in LPS-stimulated PBMC. Some of lymphocytes showed positive immunoreactivity to TGF-beta. Double immunohistochemical stain showed that IL-1beta, IL-6, TNF-alpha expression was not associated with CD14 postivity on monocytes. IL-1beta, IL-6, TNF-alpha and TGF-/betamRNA expression worn same as observed in immunoreactivity for each cytokines. CONCLUISON: When monocytes are stimulted with LPS under serum-free conditions, IL-6 and TNF-alphaare secreted in early stage of inflammation. In contrast, the secretion of TGF-beta arise in the late stages and that N maintained after 96 his. The main cells releasing lL-1beta, IL-6, INF-alpha and TGF-beta are monocytes, but also lymphocytes can secret TGF-beta.

The Effects of Proinflammatory Cytokines and TGF-beta, on The Fibroblast Proliferation / 결핵

BACKGROUNDS: The injury of a tissue results in the infalmmation, and the imflammed tissue is replaced by the normal parenchymal cells during the process of repair. But, constitutional or repetitive damage of a tissue causes the deposition of collagen resulting in the loss of its function These lesions are found in the lung of patients with idiopathic pulmonary fibrosis, complicated fibrosis after diffuse alveolar damage (DAD) and inorganic dust-induced lung fibrosis. The tissue from lungs of patients undergoing episodes of active and/or end-stage pulmonary fibrosis shows the accumulation of inflammatory cells, such as mononuclear cells, neutrophils, mast cells and eosinophils, and fibroblast hyperplasia. In this regard, it appears that the inflammation triggers fibroblast activation and proliferation with enhanced matrix synthesis, stimulated by inflammatory mediators such as interleukin-1 (lL-1) and/or tumor necrosis factor (TNF). It has ken well known that TGF-beta enhance the proliferation of fibroblasts and the production of collagen and fibronectin, and inhibit the degradation of collgen. In this regard, It is likely that TGF-beta undergoes important roles in the pathogenesis of pulmonary fibrosis. Nevertheless, this single cytokine is not the sole regulator of the pulmonary fibrotic response. It is likely that the balance of many cytokines including TGF-beta, IL-1, IL-6 and TNF-alpha regulates the pathogenesis of pulmonary fibrosis. In this study, we investigate the interaction of 'PGF-beta, IL-1beta, IL-6 and TNF-alpha and their effect on the proliferation of fibroblasts. METHODS: We used a human fibroblast cell line, MRC-5 (ATCC). The culture of MRC-5 was confirmed by immunofluorecent staining. First we determined the concentration of serum in cuture medium, in which the proliferation of MRC-5 is supressed but the survival of MRC-5 is retained. Second, we measured optical density after staining the cytokine-stimulated cells with 0.5% naphthol blue black in order to detect the effect of cytokines on the proliferation of MRC-5. RESULT: In the medium containg 0.5% fetal calf serum, the proliferation of MRC-5 increased by 50%, and it was maintained for 6 days. IL-1beta, TNF-alpha and IL-6 induced the proliferation of MRC-5 by 45%, 160% and 120%, respectively. IL-1beta and TNF-a enhanced TGF-beta-induced proliferation of MRC-5 by 64% and 159%, but IL-6 did not affect the TGF-beta-induced proliferation. And TNF-alpha-induced proliferation of MRC-5 was reduced by IL-1beta in 50%. TGF-beta, TNF-alpha and both induced the proliferation of MRC-5 to 89%, 135% and 222 %, respectively. CONCLUSIONS: TNF-alpha TGF-beta and lL-1beta, in the order of the effectiveness, showed the induction of MRC-5 proliferation of MRC-5. TNF-alpha and IL-1beta enhance the TGF-beta-induced proliferation of MRC-5, but IL-6 did not have any effect. TNF-alpha-induced proliferation of MRC-5 is diminished by IL-i, and TNF-alpha and TGF-beta showed a additive effect.

A Case of Bronchocentric Granulomatosis Associated with Aspergillus / 결핵

Bronchocentric granulomatosis(BCG), first defined in 1973, consists of granulomatous replacement of bronchial mucous membrane, often with heavy eosinophilic reaction within and about the involved bronchi. Etiologic factors are from hypersensitivity reaction for aspergillus, most often from idiopathic form, and in others from being associated with mycobacterium, ecchinococcus, rheumatoid disease, ankylosing spodylitis, and glomerulonephritis. Diagnosis is responsible only for pathologic findings and, in many cases, is confirmed in postoperative findings with misleading for tumor, tuberculosis, infectious or Wegener's granulomatosis. We report a case of bronchocentric granulomatosis associated with aspergillus.

A case of parsely dependent sxercise-induced anaphylaxsis / 천식및알레르기

Exercise-induced anaphylaxis can be associated with ingestion of a specific food. We experienced a case of exercise-induced anaphylaxis followed by ingestion of parsely. A 22- year old female patient was presented with angioedema of the face and chest tightness induced by running after ingestion of parsley within 15 minutes. She had suffered from allergic rhinitis. She had positive reactions to mugwort pollen and parsely extract on skin prick test in a dose dependent manner. Although the oral provocation test with parsely could not induce bronchoconstriction, we could diagnosed as parsely dependent exercise induced anaphylaxis based upon skin prick test and history.

Intracellular signal transduction of interleukin-6 production bylipopolysaccharide-stimulated fibroblasts / 대한내과학회지

OBJECTIVES: Stimulation of cell results in a variety of early biochemical events, known as signal transduction pathway and ultimately leads to final outcome like cell proliferation or cytokine production. The intracellular signal transduction pathway of IL-6 production by LPS stimulated fibroblast is not well defined. In present study, we investigated what signal transduction pathway is involved in IL-6 production. METHODS: We examined the effects of various inhi bitors of signal transduction pathway including pertussis toxin, cholera toxin, genistein, indomethacin, EDTA, nife dpine, sphingosine, staurosporine, and H8 on the produc tion of IL-6 by human fetal fibroblast MRC-5 after stimulation with LPS. IL-6 was measured by bioassay in supernatant of LPS stimulated fibroblast MRC-5 after pretreatment with inhibitors. RESULTS: Calcium inhibitor (EDTA) and protein kinase inhibitor (staurosporine) reduced IL-6 production by LPS stimulated fibroblast. Protein tyrosine kinase inhibitor(Genistein) and PKC inhibitor(sphingosine) had no influence on IL-6 production. Cholera toxin and pro staglandin inhibitor (indomethacin) led to increase in IL-6 production by LPS stimulated fibroblasts. CONCLUSION:: These results suggest that G protein associated receptors, through the calcium dependent pathway, are working in IL-6 production by LPS stim ulated fibroblasts.

Perspective of Bronchial Responsiveness According to an Inhaled Anti-inflammatory Treatment in Cough Asthma / 결핵

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 coulee 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 (400microgram 2/day), twenty-two entered nedocromil (4mg2/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.

Airway hyperresponsiveness and etiology in patients with chronic cough / 결핵

BACKGROUND:Chronic cough is commomly defined as a persistent or recurrent cough exceeding 3 week's duration. The prevalence of chroinc cough is reported to range from 14% to 23% for nonsmoking adults. The post nasal drip syndrome has been determined to be the most common cause of chronic cough, followed by asthma, chronic bronchitis, gastroesophageal reflux and bronchiectasis. Cough can be the only manifestation of asthma.. Bronchial provocation tests are useful in diagnosing cough variant asthma. We investigated the clinical or laboratory findings and the incidence of airway hyperresponsiveness and evaluated the etiology in patients with chronic cough. METHOD: We evaluated 46 patients with chronic cough. Methacholine challenge test were done. RESULTS: The results were as follows : 1) Thirty - five percent(16/46) of the chronic cough patients and 44% of the post nasal drip syndrom(7/16) showed the positive responses to methacholine challenge test. 2) The underlying causes of chronic cough were post nasal drip syndrome in 35%, bronchitis in 21.7%, cough-variant asthma in 17.4%, and unknown condition in 25.9%. 3) Airway hyperresponsiveness in chronic cough was not related to respiratory symptom, nasal symptom, post nasal drip, smoking, derangement of ventilatory function, atopy, or sinusitis. CONCLUSION: Airway hyperresponsivenss in patients with chronic cough increased in frequency when compaired with normal control, allergic rhinitis. Cough-variant asthma account for 17.4% of patients with chronic cough.

Time Course Change of Phagocytes and Proinflammatory activities in BALF in Endotoxin-induced Acute Lung Injury / 결핵

BACKGROUND: Severe acute lung injury(ALI), also known as the adult respiratory distress syndrome(ARDS), is a heterogenous nature of dynamic and explosive clinical synrome that exacts a mortality of approximately 50%. Endotoxin(ETX) is an abundant component of the outer membrane of gram-negative bacteria capable of inducing severe lung injury in gram-negative sepsis and gram-negative bacterial pneumonia, which are among the most common predisposing causes of ARDS. The influx of PMNs into airway tissue is a pathological hallmark of LPS-induced lung injury. And th3re is a substantial evidence suggesting that cytokines are important mediators of lung injury in gram-negative sepsis. However, the kinetics of phagocytes and cytokines by an exact time sequence and their respective pathogenic importance remain to be elucidated. This study was performed to investigate the role of phagocytes and proinflammatory cytokines in ETX-induced ALl through a time course of changes in the concentration of protein, TNFa and IL-6, and counts of total and its differential cells in BALF. The consecutive histologic findings were also evaluated. METHOD: The experimental animals, healthy male Sprague-Dawley, weighted 200+/-50g, were divided into controland ALI-group. ALI was induced by an intravenous administration of ETX, 5mg/kg. Above mentioned all parameters were examined at 0(control), 3, 6, 24, 72 h after administration of ETX. TNFa and IL-6 conc. in BALE were measured by a bioassay. RESULTS: The protein concentration and total leukocyte count(TC) in BALF was significantly increased at 3h compared to controls(p<0.05). The protein conc. was significantly elavated during observation period, but TC was significantly decreased at 72h(p<0.05 vs. 24h). There was a close relationship between TC and protein cone. in BALF(r = 0.65, p <0.001). The PMN and monocyte count was well correlated with TC in BALF, and the correlation of PMN(r=0.97, p<0.001) appeared to be more meaningful than that of monoeyte(r = 0.61, p<0.001). There was also a significant correlation between protein cone. and PMN or monocyte count in BALF(PMN vs. monocyte r = 0.55, p<0.005 vs. r = 0.64, p<0.001). The count of monocyte was significantly elavated during observation period though a meaningful reduction of PMN count in BALF at 72h, this observation suggested that monocyte may, at least, partipate in the process of lung injury steadly. In this sudy, there was no relationship between IL-6 and TNFt conc., and TNFa but not IL-6 was correlated with TC(r 0.61, p <0.05) and monocyte(r = 0.67, p<0.05) in BALF only at 3, 6h after ETX introduced. In particular, the IL-6 cone. increased earlier and rapidly peaked than TNFz cone. in BALF. In histologic findings, the cell counts of lung slices were increased from 3 to 72h(p<0.001 vs. NC). Alveolar wallthickness was increased from 6 to 24h(p<0.001 vs. NC). There was a significant correlation between the cell counts of lung slices and alveolar wall-thickness(r= 0.61, p<0.001). This result suggested that the cellular infiltrations might be followed by the alterations of interstitium, and the edematous change of alveolar wall might be most rapidly recovered to its normal condition in the process of repair. CONCLUSION: We concluded that although the role of PMIN is partly certain in ETX-induced ALI, it is somewhat inadequate to its known major impact on ALL Alveolar macrophage and/or non-immune cells such as pulmonary endothelial or epithelial cells, may be more importantly contributed to the initiation and perpetual progression of ETX-induced ALI. The IL-6 in ETX-induced ALI was independent to TNFa, measured by a bioassay in BALF. The early rise in IL-6 in BALF implies multiple origins of the IL-6.