• Advances in Traditional Medicine
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• v.8 no.1
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• pp.1-16
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• 2008

Immunity is responsible for the defense mechanism of the body but in case of autoimmune diseases, its role gets diverted. Like so many other diseases, asthma is also considered as one of the most common autoimmune diseases to be occurring in community. Asthma is defined as a chronic inflammatory airway disease that is characterized by airway hyper reactivity and mucus hypersecretion that result in intermittent airway obstruction. The incidence of allergic asthma has almost doubled in the past two decades. Although, precise causative mechanism of asthma is unknown, but several mechanisms have been proposed that is immunological, pharmacological and genetic mechanisms, and airway and neurogenic inflammation. The inflammatory process observed in the asthmatic patients is the final result of a complex network of interactions between various immunological cell lineages, its mediators and secreted substances. Thus, among the mechanisms proposed, the immunological one plays a key role. Through this article, we have tried to provide some insight into immunological mechanisms in pathogenesis of asthma.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.6
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• pp.1636-1648
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• 2006

There are detailed descriptions of the clinical experiences and prescriptions of asthma in traditional Korean medicine. Zedoariae rhizoma is one of the Korean herbal medicines used to treat bronchial asthma and allergic rhinitis for centuries. However, the therapeutic mechanisms of this medication are still far from clear, In this study, a house-dust-mite (Dermatophagoides pteronyssinus [Der p])-sensitized murine model of asthma was used to evaluate the immunomodulatory effect of Zedoariae rhizoma on the allergen-induced airway inflammation in asthma. Three different protocols were designed to evaluate the treatment and/or long-term prophylacitic effect of Zedoariae rhizoma in Der p-sensitized mice. Cellular infiltration and T-cell subsets in the bronchoalveolar lavage fluid (BALF)of allergen-challenged mice were analyzed. Intrapulmonary lymphocytes were also isolated to evaluate their response to allergen stimulation. When Zedoariae rhizoma was administered to the sensitized mice before AC (groups A and C), it suppressed airway inflammation by decreasing the number of total cells and eosinophil infiltration in the BALF, and downregulated the allergen- or mitogen-induced intrapulmonary lymphocyte response of sensitized mice as compared to those of controls. This immunomodulatory effect of Zedoariae rhizoma may be exerted through the regulation of T-cell subsets by elevation or activation of the CD8+ and double-negative T-cell population in the lung. However, the administration of Zedoariae rhizoma to sensitized mice 24 h after AC (group B) did not have the same inhibitory effect on the airway inflammation as Zedoariae rhizoma given before AC. Thus, the administration of Zedoariae rhizoma before AC has the immunomodulatory effect of reducing bronchial inflammation in the allergen-sensitized mice. On the other hand, to determine the potentiality of prophylactic and/or therapeutic approaches using a traditional herbal medicine, Zedoariae rhizoma, for the control of allergic disease, we examined the effects of oral administration of Zedoariae rhizoma on a murine model of asthma allergic responses. When oral administration of Zedoariae rhizoma was begun at the induction phase immediately after OVA sensitization, eosinophilia and Th2-type cytokine production in the airway were reduced in OVA-sensitized mice following OVA inhalation. These results suggest that the oral administration of Zedoariae rhizoma dichotomously modulates allergic inflammation in murine model for asthma, thus offering a different approach for the treatment of allergic disorders.

• The Korean journal of internal medicine
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• v.33 no.6
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• pp.1210-1223
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• 2018

Background/Aims: The co-occurrence of obesity aggravates asthma symptoms. Diet-induced obesity increases helper T cell (TH) 17 cell differentiation in adipose tissue and the spleen. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pravastatin can potentially be used to treat asthma in obese patients by inhibiting interleukin 17 (IL-17) expression. This study investigated the combined effects of pravastatin and anti-IL-17 antibody treatment on allergic inflammation in a mouse model of obesity-related asthma. Methods: High-fat diet (HFD)-induced obesity was induced in C57BL/6 mice with or without ovalbumin (OVA) sensitization and challenge. Mice were administered the anti-IL-17 antibody, pravastatin, or both, and pathophysiological and immunological responses were analyzed. Results: HFD exacerbated allergic airway inflammation in the bronchoalveolar lavage fluid of HFD-OVA mice as compared to OVA mice. Blockading of the IL-17 in the HFD-OVA mice decreased airway hyper-responsiveness (AHR) and airway inflammation compared to the HFD-OVA mice. Moreover, the administration of the anti-IL-17 antibody decreased the leptin/adiponectin ratio in the HFD-OVA but not the OVA mice. Co-administration of pravastatin and anti-IL-17 inhibited airway inflammation and AHR, decreased goblet cell numbers, and increased adipokine levels in obese asthmatic mice. Conclusions: These results suggest that the IL-17-leptin/adiponectin axis plays a key role in airway inflammation in obesity-related asthma. Our findings suggest a potential new treatment for IL-17 as a target that may benefit obesity-related asthma patients who respond poorly to typical asthma medications.

• IMMUNE NETWORK
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• v.21 no.4
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• pp.26.1-26.28
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• 2021

Asthma exacerbations are a major cause of intractable morbidity, increases in health care costs, and a greater progressive loss of lung function. Asthma exacerbations are most commonly triggered by respiratory viral infections, particularly with human rhinovirus (hRV). Respiratory viral infections are believed to affect the expression of indoleamine 2,3-dioxygenase (IDO), a limiting enzyme in tryptophan catabolism, which is presumed to alter asthmatic airway inflammation. Here, we explored the detailed role of IDO in the progression of asthma exacerbations using a mouse model for asthma exacerbation caused by hRV infection. Our results reveal that IDO is required to prevent neutrophilic inflammation in the course of asthma exacerbation caused by an hRV infection, as corroborated by markedly enhanced Th17- and Th1-type neutrophilia in the airways of IDO-deficient mice. This neutrophilia was closely associated with disrupted expression of tight junctions and enhanced expression of inflammasome-related molecules and mucin-inducing genes. In addition, IDO ablation enhanced allergen-specific Th17- and Th1-biased CD4⁺ T-cell responses following hRV infection. The role of IDO in attenuating Th17- and Th1-type neutrophilic airway inflammation became more apparent in chronic asthma exacerbations after repeated allergen exposures and hRV infections. Furthermore, IDO enzymatic induction in leukocytes derived from the hematopoietic stem cell (HSC) lineage appeared to play a dominant role in attenuating Th17- and Th1-type neutrophilic inflammation in the airway following hRV infection. Therefore, IDO activity in HSC-derived leukocytes is required to regulate Th17- and Th1-type neutrophilic inflammation in the airway during asthma exacerbations caused by hRV infections.

• The Korea Journal of Herbology
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• v.26 no.4
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• pp.49-57
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• 2011

Objective : Allergic asthma is a chronic airway disease that affects millions of people in the developed world. The disease is characterized by concurring airway inflammation, Th2 cytokine production, increased mucus secretion, airway hyperresponsiveness (AHR) to inhaled antigen, and pulmonary fibrosis. To investigate the therapeutic and anti-asthmatic effects of Drynariae Rhizoma (DR), we examined the influence of DR on the development of pulmonary eosinophilic inflammation and airway hyperresponsiveness in a mouse model of allergic asthma. Methods : In this study, BALB/c mice were systemically sensitized to ovalbumin (OVA) followed intratracheally, intraperitoneally, and by aerosol allergen challenges. We investigated the effect of DR on airway hyperresponsiveness, pulmonary eosinophilic infiltration, various immune cell phenotypes, Th2 cytokine production and OVA specific IgE production in a mouse model of asthma. Results : In asthmatic mice, we found that DR.treated groups had suppressed eosinophil infiltration, allergic airway inflammation and AHR by suppressing the production of IL-5, IL-13 and OVA specific IgE. Conclusions : Our data suggest that the therapeutic mechanism by which DR effectively treats asthma is based on reductions of Th2 cytokines (IL-5), eotaxin, OVA-specific IgE production and eosinophil infiltration.

• IMMUNE NETWORK
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• v.22 no.6
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• pp.45.1-45.15
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• 2022

Asthma is a chronic airway inflammatory disease characterized by reversible airway obstruction and airway hyperreactivity to various environmental stimuli, leading to recurrent cough, dyspnea, and wheezing episodes. Regarding inflammatory mechanisms, type 2/eosinophilic inflammation along with activated mast cells is the major one; however, diverse mechanisms, including structural cells-derived and non-type 2/neutrophilic inflammations are involved, presenting heterogenous phenotypes. Although most asthmatic patients could be properly controlled by the guided treatment, patients with severe asthma (SA; classified as a treatment-refractory group) suffer from uncontrolled symptoms with frequent asthma exacerbations even on regular anti-inflammatory medications, raising needs for additional controllers, including biologics that target specific molecules found in asthmatic airway, and achieving the precision medicine for asthma. This review summarizes the immunologic basis of airway inflammatory mechanisms and current biologics for SA in order to address unmet needs for future targets.

• Tuberculosis and Respiratory Diseases
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• v.81 no.1
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• pp.80-87
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• 2018

Background: Asthma is a disease of chronic airway inflammation with heterogeneous features. Neutrophilic asthma is corticosteroid-insensitive asthma related to absence or suppression of $T_H2$ process and increased $T_H1$ and/or $T_H17$ process. Macrolides are immunomodulatory drug that reduce airway inflammation, but their role in asthma is not fully known. The purpose of this study was to evaluate the role of macrolides in neutrophilic asthma and compare their effects with those of corticosteroids. Methods: C57BL/6 female mice were sensitized with ovalbumin (OVA) and lipopolysaccharides (LPS). Clarithromycin (CAM) and/or dexamethasone (DXM) were administered at days 14, 15, 21, 22, and 23. At day 24, the mice were sacrificed. Results: Airway resistance in the OVA+LPS exposed mice was elevated but was more attenuated after treatment with CAM+DXM compared with the monotherapy group (p<0.05 and p<0.01). In bronchoalveolar lavage fluid study, total cells and neutrophil counts in OVA+LPS mice were elevated but decreased after CAM+DXM treatment. In hematoxylin and eosin stain, the CAM+DXM-treated group showed less inflammation additively than the monotherapy group. There was less total protein, interleukin 17 (IL-17), interferon ${\gamma}$, and tumor necrosis factor ${\alpha}$ in the CAM+DXM group than in the monotherapy group (p<0.001, p<0.05, and p<0.001). More histone deacetylase 2 (HDAC2) activity was recovered in the DXM and CAM+DXM challenged groups than in the control group (p<0.05). Conclusion: Decreased IL-17 and recovered relative HDAC2 activity correlated with airway resistance and inflammation in a neutrophilic asthma mouse model. This result suggests macrolides as a potential corticosteroid-sparing agent in neutrophilic asthma.

• Journal of Korean Academic Society of Home Health Care Nursing
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• v.26 no.3
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• pp.288-299
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• 2019

Purpose: This study was conducted to identify factors influencing asthma, with a focus on obesity and systemic inflammation, in Korean adults. Methods: This study was a secondary analysis of data from the sixth Korea National Health and Nutrition Examination Survey (2015). A total of 3,693 individuals aged ≥19 years were included. The prevalence of asthma was 1.6% in the normal weight group (n=23), 1.4% in the overweight group (n=13), and 2.9% in the obese group (n=39). Data included markers associated with systemic inflammation such as high sensitivity C-reactive protein level, leukocyte count, hemoglobin level, and hematocrit value based on previous studies. The results were analyzed using a complex sampling design analysis and by multiple logistic regression analysis with SPSS WIN 24.0 program. Results: In the obese group, age between 50 and 59 years (adjusted odds ratio [AOR]=14.06, 95% confidence interval [CI]=1.84-27.14); age between 60 and 69 years (AOR=3.30, 95% CI=1.34-8.14); age ≥70 years (AOR=3.22, 95% CI=1.31-7.93); female gender (AOR=2.32, 95% CI=1.12-4.78); leukocyte count (AOR=1.18, 95% CI=1.01-1.38), and hemoglobin levels (AOR=0.60, 95% CI=0.45-0.81) were identified as factors influencing asthma. Conclusion: The results can be used to develop nursing interventions to prevent asthma associated with obesity in hospitals or home-based healthcare settings.

• Tuberculosis and Respiratory Diseases
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• v.71 no.2
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• pp.106-113
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• 2011

Background: While asthma control is defined as the extent to which the various manifestations of asthma are reduced by treatment, current guidelines of asthma recommend assessment of asthma control without consideration of airway inflammation. Our aim was to investigate the relationships between fractional exhaled nitric oxide (FeNO), a reliable marker of airway inflammation, and levels of asthma control in patients treated with inhaled corticosteroids (ICS). Methods: We enrolled 71 adult patients with asthma who had been treated with ICS for more than four months. FeNO was measured and spirometry was performed at the time of enrollment. Asthma control was assessed (a) by the physician based on the Global Initiative for Asthma guidelines, (b) by the patients, and (c) by using the Asthma Control Test (ACT). Statistical analyses were done to analyze the relationships between (i) FeNO and (ii) measures of asthma control and clinical indices for asthma manifestations. Results: There was no significant difference in FeNO levels between the three groups according to levels of asthma control (controlled, partly controlled and uncontrolled) as determined by the physician (p=0.81), or by the patients (p=0.81). In addition, FeNO values were not significantly correlated with the ACT scores (r=0.031, p=0.807), while FeNO showed a correlation with peripheral blood eosinophil counts (p<0.001). Conclusion: These findings demonstrate that FeNO levels are not associated with measures of asthma control in patients treated with ICS. Information on airway inflammation from FeNO concentrations seems to be unrelated to levels of asthma control

• Clinical and Experimental Pediatrics
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• v.48 no.3
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• pp.251-259
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• 2005

Atopy is a highly prevalent and serious health problem. The prevalence and severity of asthma and allergic diseases have increased over recent decades, particularly in industrialized nations. Early life infections may protect against the development of atopy and allergic diseases like asthma. The inverse relationship between the incidence of atopy and childhood infections has led to the 'hygiene hypothesis', which suggests that diminished exposure to childhood infections in modern society has led to decreased Th1-type responses. Th1 and Th2 responses are counter-regulatory. Reduced Th1 may lead to enhanced Th2-type inflammation, which is important in promoting asthma and allergic disease via up-regulation of IL-4, IL-5, and IL-13. It is now widely accepted that altered regulation of Th2 responses(and possibly the balance between Th1 and Th2 responses) is an important factor in the development of atopy. CpG DNA represent a novel class of drugs with substantial immunomodulatory properties. CpG DNA contain unmethylated motifs centered on the CpG dinucleotides, like bacterial DNA. These CpG DNA promote Th1 and regulatory type immune responses and suppress Th2 responses. In murine studies, CpG DNA are effective in prevention and treatment of asthma and allergic diseases. CpG DNA are just beginning to be tested in human asthma. While its precise mechanisms continue to be fully studied, CpG DNA offers considerable promise as a novel treatment for atopic inflammation. It may prove to be an important disease modifying therapy, or even curative therapeutic agent for asthma and allergic diseases.