Characteristics of Proinflammatory Cytokines and Chemokines in Airways of Asthmatics: Relationships with Disease Severity and Infiltration of Inflammatory Cells (original) (raw)
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Role of Cytokines and Chemokines in the Outcome of Children With Severe Asthma
Journal of Pediatrics Review
Context: Asthma, characterized by airway inflammation, is a common chronic disease of childhood. Cytokines and chemokines could be used in the diagnosis, treatment, and management of asthma severity in children. In this review, we have explained the application of cytokines and chemokines as biomarkers in pediatric asthma. Evidence Acquisition: All related articles were separately searched by two researchers using the following keywords in PubMed, Scopus, and Embase databases: Cytokine biomarkers, chemokines biomarkers, and children asthma. Articles published from 2000 to 2017 were investigated in the research, and 28 articles were included in the final analysis for this review. Results: About cytokines, serum Interleukin 4 (IL-4) level is a marker of the presence of asthma, and IL-13 is a key cytokine involved in the manifestation of asthma symptoms. High IL-13 concentration and number of IL-13+ cells in the bronchial submucosa specimens are characteristic of severe asthma. Serum IL-5 concentration 3.1 times in children with severe asthma. IL-17 is involved in airway obstruction. IFN-γ gene polymorphism (+874A/T) in children elevates susceptibility to asthma. TGFB1 polymorphisms are considered as indicators of asthma severity. IL-26 plays an important role in asthma severity. IP-10 may be a useful inflammatory marker of asthma severity. High periostin level has been identified in pediatric asthma. PDGF level, which is high in asthma patients, plays an important role in bronchial fibrosis. About chemokines, plasma TARC concentration may be a useful biomarker of airway inflammation and asthma severity in children. Studies have supported the association between high serum RANTES levels and severe airway obstruction in children. CXCR4 levels are high in pediatric asthma and are associated with disease severity. Conclusions: A wide range of cytokines and chemokines may play important roles in asthma severity in pediatric patients. Therefore, several studies have recommended the use of multiple molecular biomarkers, such as cytokines, for determining asthma severity in children.
Differences in Airway Cytokine Profile in Severe Asthma Compared to Moderate Asthma
Chest, 2008
Background: Some studies of severe asthma suggest that persistence or alteration in the pattern of inflammation may be associated with the severity of the disease. Whether there are differences in the expression of the principal cytokines and chemokines relevant to eosinophilic and neutrophilic inflammation in the airway tissues of severe compared to moderate asthmatics has not been determined. The aim of this study was to compare the patterns of expression of representative T-helper (Th) type 1 (interferon [IFN]-␥) and Th-2 cytokines (interleukin [IL]-4, IL-5) and the neutrophil-and eosinophil-associated chemokines (IL-8 and eotaxin) in the airway tissues of patients with severe and moderate asthma. Methods: Subjects with severe asthma (n ؍ 24) and a comparison moderate asthma group (n ؍ 26) were assessed using spirometry, induced sputum, exhaled nitric oxide, and bronchial biopsy. The expression of proteins of interest in the epithelium and subepithelium of the airway wall was examined by immunocytochemistry. Results: Subjects with severe asthma were more symptomatic, had a lower FEV 1 , and had more sputum neutrophilia (p ؍ 0.007) and eosinophilia (p ؍ 0.001). Exhaled nitric oxide was similar between groups. IL-8 and IFN-␥ expression were increased and IL-4 expression was decreased in severe asthma compared to moderate disease (p < 0.001 for each comparison). Eotaxin and IL-5 expression did not differ between the groups. Conclusion: Patients with severe asthma have increases in neutrophils and eosinophils in the sputum, and differ in airway cytokine/chemokine expression from moderate asthmatics. Excess neutrophilia may be explained by increased expression of IL-8, but differences in eosinophilia do not appear to be associated with IL-5 and eotaxin expression.
Brazilian Journal of Medical and Biological Research, 2005
Asthma and chronic obstructive pulmonary disease (COPD) are common respiratory illnesses characterized by chronic inflammation of the airways. The characterization of induced or spontaneously produced sputum is a useful technique to assess airway inflammation. In the present study, we compared the concentrations of CCL2, CCL11, CXCL8, and tumor necrosis factor-alpha (TNF-alpha) in plasma and induced sputum of patients with severe asthma or COPD and correlated the levels of these mediators with inflammatory cells in sputum. Asthmatic patients had elevated levels of eosinophils (40.1 +/- 6.24%) in sputum whereas neutrophils (63.3 +/- 4.66%) predominated in COPD patients. The levels of the chemokine CCL11 were markedly increased in sputum (708.7 +/- 330.7 pg/ml) and plasma (716.6 +/- 162.2 pg/ml) of asthmatic patients and correlated with the percentage of eosinophils in induced sputum. The concentrations of CXCL8 (817.0 +/- 105.2 pg/ml) and TNF-alpha (308.8 +/- 96.1 pg/ml) were higher in sputum of COPD patients and correlated with the percentage of neutrophils in induced sputum. There was also an increase in the concentrations of CXCL8 (43.2 +/- 6.8 pg/ml) in sputum of asthmatic patients. These results validate that sputum is a suitable method to assess chemokines and cytokines associated with asthma and COPD. Moreover, the mechanisms involved in the synthesis of CCL11 and CXCL8/TNF-alpha would be helpful to better understand the inflammatory profile associated with asthma and COPD, respectively.
Role of epithelial chemokines in the pathogenesis of airway inflammation in asthma (Review)
Molecular medicine reports, 2018
As the first barrier to the outside environment, airway epithelial cells serve a central role in the initiation and development of airway inflammation. Chemokines are the most direct and immediate cell factors for the recruitment and migration of inflammatory cells. The present review focused on the role of epithelial chemokines in the pathogenesis of airway inflammation in asthma. In addition to traditional CC family chemokines and CXC family chemokines, airway epithelial cells also express other chemokines, including thymic stromal lymphopoietin and interleukin‑33. By expressing and secreting chemokines, airway epithelial cells serve a key role in orchestrating airway inflammation in asthma.
Scandinavian Journal of Immunology, 2017
This study was aimed to determine the profiles of serum cytokines (IL-1b, TNFa, IL-4, IL-5) and chemokines (MCP-1: monocyte chemoattract protein-1 and RANTES: regulated on activation normal T cell expressed and secreted) in individuals with an asthmatic versus a non-asthmatic background with bacterial, viral or mixed acute respiratory infection. Asthmatic (n = 14) and non-asthmatic (n = 29) patients with acute viral, bacterial or mixed (bacterial and viruses) respiratory infection were studied. Patients were also analysed as individuals with pneumonia or bronchitis. Healthy individuals with similar age and sex (n = 10) were used as controls. Cytokine/chemokine content in serum was determined by ELISA. Increased cytokine/chemokine concentration in asthmatic and nonasthmatic patients was observed. However, higher concentrations of chemokines (MCP-1 and RANTES) in asthmatic patients infected by viruses, bacteria or bacteria and viruses (mixed) than in non-asthmatic patients were observed. In general, viral and mixed infections were better cytokine/chemokine inducers than bacterial infection. Cytokine/chemokine expression was similarly increased in both asthmatic and non-asthmatic patients with pneumonia or bronchitis, except that RANTES remained at normal levels in bronchitis. Circulating cytokine profiles induced by acute viral, bacterial or mixed lung infection were not related to asthmatic background, except for chemokines that were increased in asthmatic status. a Values were obtained in asthmatic (n = 10) and non-asthmatic (n = 29) including viral, bacterial and mixed infections.
Selected CC and CXC chemokines in children with atopic asthma
Advances in Dermatology and Allergology, 2016
Introduction: There are only limited data on CC and CXC chemokines regulation in children with asthma. Aim: We compared the serum profile of selected CC and CXC chemokines in patients with atopic asthma and healthy children. Material and methods: Serum concentration of CC chemokines RANTES, MCP-1, and CXC chemokines IP-10, MIG, IL-8, RANTES was measured using cytometric bead array in 44 children with atopic asthma and 17 healthy subjects. Results: The concentration of RANTES was significantly higher and the MIG level was lower in all children with asthma as compared to their control counterparts. We observed increased RANTES and decreased MIG levels also in patients with stable asthma when compared with children in the control group. The IP-10 concentration was similar between the whole asthma group and healthy controls, while significantly increased levels of this chemokine in acute asthma have been observed when compared to stable asthma. For MCP-1 and IL-8, the serum concentration was similar in all compared groups. The MIG concentration correlated positively with IP-10, IL-8, and CRP levels and negatively with the eosinophil count. A negative correlation between the IP-10 and eosinophil count and a negative correlation between FEV 1 and IP-10 were found. Conclusions: An increased serum RANTES level in children with asthma may result in enhancement of Th2 lymphocyte recruitment into the airway. A decreased expression of Th1 chemokine MIG in children with stable asthma may contribute to a diminished antagonizing effect on Th2 cytokine production and hence intensify Th2 predominance. An increased IP-10 level in children during an asthma attack suggest that this chemokine is a serological marker of disease exacerbation.
Journal of Allergy and Clinical Immunology, 2006
Background: Simultaneous monitoring of airway inflammation and physiology might be useful for asthma management. Objective: We examined the upregulated molecules in asthmatic airways. Furthermore, we investigated the relationship between these molecules and the airway physiologic properties of asthma. Methods: Ten nonsmoking healthy subjects and 16 steroidnaive asthmatic patients were enrolled. Exhaled breath condensate (EBC) sampling, spirometry, and methacholine inhalation challenge were performed on one occasion in this cross-sectional study. Peak expiratory flow was also measured for 4 weeks. Airway cytokine-chemokine-growth factor production was analyzed with a protein array. Results: The expressions of IL-4, IL-8, IL-17, TNF-a, RANTES, IFN-g-inducible protein 10, TGF-b, and macrophage inflammatory protein 1a and 1b were significantly upregulated in asthmatic airways compared with those of nonsmoking healthy subjects. Among the upregulated molecules, RANTES expression was significantly correlated with the parameters that represent airway caliber, FEV 1 and respiratory resistance values. In addition, the levels of both TNF-a and TGF-b were significantly correlated with the methacholine threshold and peak expiratory flow variability for the week. Conclusion: Inflammatory molecule analysis with EBC appeared to be useful for monitoring the asthmatic airway condition. Clinical implications: Measurements of cytokine levels in EBC might be a promising approach to assess the efficacy of pharmacologic interventions and to investigate the pathophysiology of asthma. (J Allergy Clin Immunol 2006;118:84-90.)