scholarly journals CYTOKINES PROFILE IN BLOOD IN SEVERE ASTHMA PATIENTS WITH OBESITY

2013 ◽  
Vol 10 (6) ◽  
pp. 13-19
Author(s):  
E A Sobko ◽  
I A Soloveva ◽  
O P Ischenko ◽  
A Y Kraposhina ◽  
I V Demko ◽  
...  

Background. To study the cytokines profile in the peripheral blood of patients with severe asthma and obesity. Methods.139 patients with severe bronchial asthma have been examined, including 66 patients with severe bronchial asthma and body mass index (BMI) 30 (2nd group). The control group was formed from 40 healthy volunteers. The respiratory function, the cytokine integral index and the levels of TNFα, IL4, IL6, IL2, IL10, IFN-γ, IL8, IL17 in the peripheral blood of patients in and out of an exacerbation were studied. Results. More significant systemic inflammation signs expressed in increased levels of TNFα, IL6, IL4, IL2 and IFN-γ were found in exacerbation period of the disease. In obese patients the increased level of proinflammatory cytokine IL17 in exacerbation period was estimated. Conclusion. We have demonstrated the presence of systemic inflammation in patients with severe BA, regardless of the presence of obesity, increased level of proinflammatory cytokine IL17 in patients with severe bronchial asthma and obesity in the period of exacerbation. It can be a reason of the low effect of steroid therapy in patients with BMI >30.

2012 ◽  
Vol 9 (1) ◽  
pp. 42-49
Author(s):  
E A Sobko ◽  
A Y Kraposhina ◽  
O P Ischenko ◽  
I V Demko ◽  
A B Salmina ◽  
...  

Background. The objective of this study was to estimate a vascular wall status of large arteries and function of endothelium in patients with different clinical forms of bronchial asthma throughout the disease progression. 220 patients with bronchial asthma have been examined, including 106 persons with moderate asthma ( 1 st group), 61 persons with severe asthma (2 nd group), and 53 persons with steroid-dependent asthma. Control group was formed from 40 healthy donors. Methods. We have assessed parameters of external respiration, arterial rigidity, and the levels of TNFα, IL-6, sCD31 (sPECAM-1), CRP in the peripheral blood at the time of exacerbation and 48 weeks later. Results. We found elevation of IL-6 and TNFα levels in all the tested groups in the period of exacerbation comparing to the control group (p


Author(s):  
В.А. Белоглазов ◽  
Ю.О. Попенко ◽  
Н.А. Шадчнева ◽  
А.И. Гордиенко ◽  
В.Б. Калиберденко ◽  
...  

Актуальность. Поскольку роль эндотоксина в индукции бронхообструктивного синдрома сегодня уже не вызывает сомнений, представляется целесообразным и определение роли антиэндотоксинового иммунитета (АЭИ) в формировании различных биофенотипов хронического воспаления, которые лежат в основе особенностей течения бронхиальной астмы (БА). Цель настоящего исследования - определение роли гуморального и мукозального звеньев АЭИ и системного воспаления при различных биофенотипах воспаления у больных БА, которые могли бы быть полезны для разработки персонифицированной терапии. Материалы и методы. В исследование включены 109 больных с верифицированным диагнозом среднетяжёлой и тяжёлой бронхиальной астмы. Пациенты были разделены на 3 группы в зависимости от типа воспаления в дыхательных путях: 1-я группа - эозинофильный, 2-я группа - нейтрофильный, 3-я группа - смешанный гранулоцитарный. Гуморальное и мукозальное звенья эндотоксин-связывающих систем оценивали по уровням специфических эндотоксин-связывающих антител классов M, A, G (анти-ЭТ IgM, анти-ЭТ IgA, анти-ЭТ IgG) в периферической крови, и уровню секреторного антиэндотоксинового иммуноглобулина класса A в индуцированной мокроте. Системное воспаление оценивали по концентрации С-реактивного белка (СРБ). Результаты. При нейтрофильном и смешанном биофенотипах воспаления зарегистрированы повышенные уровни анти-ЭТ IgM и анти-ЭТ IgА в периферической крови. В то время как при эозинофильном биофенотипе воспаления не выявлено существенных различий данных показателей от контрольной группы. Концентрация анти-ЭТ IgG во всех группах больных бронхиальной астмы не отличалась от диапазона нормы. При всех биофенотипах воспаления выявлено повышение концентраций секреторного анти-ЭТ IgА и СРБ в рамках низкоинтенсивного воспаления. Наибольший уровень анти-ЭТ IgА и СРБ зарегистрирован при нейтрофильном и смешанном биофенотипах воспаления. Выявлены умеренные прямые корреляционные связи: между уровнем секреторного анти-ЭТ IgA и относительным количеством нейтрофилов в индуцированной мокроте (r = 0,469, р < 0,05); между уровнем СРБ и уровнем секреторного анти-ЭТ IgA (r = 0,427, р < 0,05). Выводы. Наиболее выраженный гуморальный и мукозальный ответ на эндотоксин и интенсивность системного воспаления при нейтрофильном и смешанном биофенотипах воспаления свидетельствуют о значительной роли ингаляционного эндотоксина в формировании тяжёлой астмы. Выявленный дисбаланс гуморального и мукозального звеньев АЭИ систем дополняет современные представления патогенеза бронхиальной астмы с различными биофенотипами воспаления, предоставляет перспективу возможности персонификации лечения и достижения контроля заболевания. Background. Since the role of endotoxin in induction of broncho-obstructive syndrome is above any doubt today, we focused on the role of anti-endotoxin immunity (AEI) in the formation of different phenotypes of chronic inflammation, which underlie characteristics of the course of asthma. The aim of this study was to determine the role of humoral and mucosal components of AEI and systemic inflammation in different inflammatory phenotypes in patients with asthma, which could be useful in developing personalized therapy. Materials and methods. The study included 109 patients with a verified diagnosis of moderate to severe asthma. All patients were divided into 3 groups depending on the type of inflammation in the respiratory tract: Group 1, eosinophilic; Group 2, neutrophilic; and Group 3, mixed granulocytic inflammation. The humoral and mucosal components of endotoxin binding systems were evaluated by levels of specific endotoxin-binding class M, A, and G antibodies (anti-ET IgM, anti-ET IgA, and anti-ET IgG) in peripheral blood and the level of secretory anti-endotoxin IgA in induced sputum. Systemic inflammation was assessed by concentration of C-reactive protein (CRP). Results. Peripheral blood concentrations of anti-ET IgM and anti-ET IgA were elevated in neutrophilic and mixed inflammatory phenotypes. At the same time, in the eosinophilic inflammatory phenotype, these indexes were not significantly different from the control group. In all groups of patients with asthma, concentrations of anti-ET IgG were similar and remained within the normal range. In all inflammatory phenotypes, concentrations of secretory anti-ET IgA and C-reactive protein were increased within the range of low-intensity inflammation. The highest levels of anti-ET IgA and CRP were found in neutrophilic and mixed inflammatory phenotypes. Levels of secretory anti-ET IgA moderately directly correlated with the relative number of neutrophilic leukocytes in induced sputum (r = 0.469, р < 0.05) and levels of CRP moderately directly correlated with levels of secretory anti-ET IgA (r = 0.427, р < 0.05). Conclusions. The most pronounced humoral and mucosal response to endotoxin and the intensity of systemic inflammation in neutrophilic and mixed inflammatory phenotypes evidenced a significant role of inhaled endotoxin in the formation of severe asthma. The observed imbalance of humoral and mucosal components in AEI systems supports modern ideas of the pathogenesis of asthma with different inflammatory phenotypes and provides a promising possibility of individualized treatment and control of the disease.


2013 ◽  
Vol 68 (7) ◽  
pp. 57-60
Author(s):  
O. A. Sharavii ◽  
S. V. Smirnova

 Aim. The study of the prevalence and clinical peculiarities of Mycoplasmosis and Chlamydiosis in patients with different pathogenic forms of bronchial asthma (BA) taking into account ethnicity of a patient. Subjects and Methods. The research covered 239 subjects – both the Europeoids and the Mongoloids in the city of Krasnoyarsk and the town of Kyzyl, all of them being BA patients of different stages, including acute stage and practically healthy. We had determined antigens Mycoplasma pneumoniae, Mycoplasma hominis, Chlamydophila pneumoniae, Chlamydophila psittaci and Chlamydia trachomatis in smears of mucosa of pharynx and antibodies to these antigens in peripheral blood serum. Results.  We found high frequency of Mycoplasmosis and Chlamydiosis in the inhabitants of Eastern Siberia, BA patients with different pathogenic forms as compared to control group. We had determined ethnic peculiarities of specific immune response: IgM to М. pneumoniae was revealed in the Europoids more frequently than in the Mongoloids, but IgM to С. pneumoniae and to C. trachomatis, C. trachomatis antigens had been revealed more often in the Mongoloids than in the Europoids. We accepted as clinical equivalents of Mycoplasmosis and Chlamydiosis diagnostics the following signs: temperature around 37C (subfebrile temperature), non-intensive but stable coughing with scanty mucous and muco-purulent sputum, dyspnea of mixed character. Conclusions. Mycoplasma and Chlamydia are meaningful etiologic factors of bronchial asthma. We have found the peculiarities of immune response depending on ethnicity of a patient (ethnic belonging). Clinical markers of Mycoplasmosis and Chlamydiosis should be taken into account in bronchial asthma in order to provide diagnostics timely as well as eradication of infection agents. Because of insufficient knowledge of problem of bronchial asthma related to contamination with Мycoplasma and Chlamydia we put the goal to study the frequency of Mycoplasmosis and Chlamydiosis occurrence in bronchial asthma patients and determine the characteristics clinical course of diseases. We defined antigens Мycoplasma pneumoniae, Мycoplasma hominis, Chlamydophila pneumoniaе, Chlamydophila psittaci, Chlamydia trachomatis in smears of oropharynx mucosa and antibodies to them in blood serum. 


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yan-Long Ren ◽  
Tao-Tao Li ◽  
Wei Cui ◽  
Li-Min Zhao ◽  
Na Gao ◽  
...  

AbstractInterferon-gamma (IFN-γ) is a cytokine involved in the pathogenesis of Takayasu’s arteritis (TAK). However, the source of IFN-γ in TAK patients is not fully clear. We aimed to investigate the source of IFN-γ in TAK. 60 TAK patients and 35 health controls were enrolled. The lymphocyte subsets of peripheral blood were detected by flow cytometry, cytokines were detected by Bio-plex. The correlation among lymphocyte subsets, cytokines and disease activity indexes was analyzed by person correlation. The level of serum IFN-γ in TAK patients was significantly increased (P < 0.05). The percentage of CD3+IFN-γ+ cells in peripheral blood CD3+ cells was significantly higher in TAK patients than that of healthy control group (P = 0.002). A higher proportion of CD3+CD8+IFN-γ+ cells/CD3+IFN-γ+ cells (40.23 ± 11.98% vs 35.12 ± 11.51%, P = 0.049), and a significantly lower CD3+CD4+IFN-γ+/ CD3+CD8+IFN-γ+ ratio (1.34 ± 0.62% vs 1.80 ± 1.33%, P = 0.027) were showed in the TAK group than that of control group. The CD3+CD8+IFN-γ+/CD3+IFN-γ+ ratio was positively correlated with CD3+IFN-γ+cells/ CD3+cells ratio (r = 0.430, P = 0.001), serum IFN-γ level (r = 0.318, P = 0.040) and IL-17 level (r = 0.326, P = 0.031). It was negatively correlated with CD3+CD4+IFN-γ+/CD3+IFN-γ+ ratio (r = − 0.845, P < 0.001). IFN-γ secreted by CD3+CD8 + T cells is an important source of serum IFN-γ in TAK patients.


Author(s):  
Irina V. Tikhonova ◽  
N. I. Kosyakova ◽  
A. V. Tankanag ◽  
N. K. Chemeris

Background: Pulmonary hemodynamic disorders depend on the inflammatory phases and severity of the obstructive syndrome. However, the effect of asthma bronchial obstruction on the state of peripheral hemodynamics remains insufficiently known. Aims: To study the effects of airway obstruction on skin blood flow parameters and its regulatory systems in patients with persistent atopic bronchial asthma in the remission state.Materials and methods: A comparative study of the skin peripheral blood flow in patients with bronchial asthma with severe airway obstruction (1st group) and without obstruction (2nd group) was conducted. 20 patients with confirmed diagnosis of atopic asthma of 50–74 years old participated in the study. All patients received basic therapy in a constant dosing of high doses of inhaled glucocorticosteroids/long-acting beta-2-agonists. The control group included 20 healthy volunteers without evidence of bronchial obstruction. The study lasted for 3 months. The forced expiratory volume in 1 s (FEV1) was used to evaluate the bronchial obstruction by spirometry technique. Skin blood perfusion changes were recorded by laser Doppler flowmetry at rest and in response to short-term local ischemia. Registered peripheral blood flow signals were examined using the amplitude temporal filtering in five frequency intervals to identify the functional features of the peripheral blood flow regulation systems. Results: Consistent two-fold decrease of the oscillation amplitudes was found in the neurogenic interval at rest (p=0.031), as well as in the myogenic (p=0.043; p=0.031) and endothelial intervals (p=0.037; p≤0.001) both at rest and during the postocclusive reactive hyperemia respectively in the 1st group of patients with bronchial obstruction (FEV1 80%) compared with the control group. No significant changes were revealed for skin blood flow parameters in the 2nd patient group (without obstruction, FEV1 80%) in comparison to control subjects.Conclusions: The presence of bronchial obstruction has a significant impact on the changes of the amplitudes of skin blood flow oscillations in patients with bronchial asthma in the myogenic, neurogenic and endothelial intervals.


2007 ◽  
pp. 56-59
Author(s):  
E. A. Starovoytova ◽  
S. N. Ivanov ◽  
L. M. Ogorodova

Asthma patients (n = 79, 7 to 17 years of age) were divided into 3 groups according to asthma severity: mild (n = 23), moderate (n = 24), and severe asthma (n = 32). Asthma was diagnosed according to GINA (2002). Echocardiography, ultrasound evaluation of endothelium vasomotor function and measurement of nitrite anion concentration in exhaled breathe condensate (EBC) were performed in the all patients. Right ventricle dilatation and increase in the total pulmonary vascular resistance were revealed only in patients with severe asthma compared to the control group. Increase in pulmonary artery systolic pressure was significantly higher in the severe asthma patients compared both to the control group and mild asthma patients. Increased right ventricle pressure was accompanied by endothelium dysfunction in 48.1 % (38 patients). High EBC nitrite anion concentration (12.11 ± 1.72 μmol/L) was revealed in asthmatic children compared to control group (3,34 ± 1,58 μmol/L). The results suggest that childhood asthma is associated with morphological and functional abnormalities of pulmonary hemodynamics and endothelium function depending on severity of the disease.


2018 ◽  
Vol 32 ◽  
pp. 205873841877924 ◽  
Author(s):  
Man Tian ◽  
Yong Ji ◽  
Tingting Wang ◽  
Wenxin Zhang ◽  
Ying Zhou ◽  
...  

Regulation of the immune response in asthma is complex. MicroRNA-126 (miR-126) expression has been implicated in this response, so we sought to determine the clinical significance of miR-126 measured in the peripheral blood. A total of 80 children with acute asthma were selected to participate in the study and were compared to 80 healthy children. The relative circulating miR-126 levels, interleukin (IL)-4 levels, and the Th17 cell percentage in the peripheral blood of children in the case group were significantly higher than those in the control group, while the interferon (IFN)-γ levels and the CD4+CD25+Treg cell percentage were significantly lower than those in the control group. Along with the aggravation of the disease, the relative levels of miR-126 and IL-4 and the percentage of Th17 cells increased gradually, while the IFN-γ levels and the CD4+CD25+Treg cell percentage decreased. The relative level of miR-126 in the peripheral blood of children with asthma was positively correlated with IL-4 and the Th17 cell percentage and was negatively correlated with IFN-γ levels, CD4+CD25+Treg cell percentage and lung function indicators. The relative level of miR-126 was correlated with the Th17 cell percentage in the peripheral blood, forced vital capacity (FVC), and forced expiratory flow (FEF)75% of the children with asthma. The relative levels of miR-126 and IL-4 and the Th17 cell percentage were positively correlated with the severity of the asthma, while IFN-γ levels and the CD4+CD25+Treg cell percentage were negatively correlated with the severity of the asthma. CD4+CD25+Treg cell percentage and relative miR-126 levels were of the most predictive value in the diagnosis of asthma. Our findings show that the overexpression of miR-126 in acute asthma is correlated with signs of immune imbalance and is predictive of the severity of the disease, suggesting that it could be used as a potential serological marker for asthma diagnosis and evaluation.


2020 ◽  
Vol 55 (5) ◽  
pp. 1802422
Author(s):  
Justine Devulder ◽  
Cécile Chenivesse ◽  
Valérie Ledroit ◽  
Stéphanie Fry ◽  
Pierre-Emmanuel Lobert ◽  
...  

Rhinovirus infections are the main cause of asthma exacerbations. As natural killer (NK) cells are important actors of the antiviral innate response, we aimed at evaluating the functions of NK cells from severe asthma patients in response to rhinovirus-like molecules or rhinoviruses.Peripheral blood mononuclear cells from patients with severe asthma and healthy donors were stimulated with pathogen-like molecules or with the rhinoviruses (RV)-A9 and RV-2. NK cell activation, degranulation and interferon (IFN)-γ expression were analysed.NK cells from severe asthma patients were less cytotoxic than those from healthy donors in response to toll-like receptor (TLR)3, TLR7/8 or RV-A9 but not in response to RV-2 stimulation. Furthermore, when cultured with interleukin (IL)-12+IL-15, cytokines which are produced during viral infections, NK cells from patients with severe asthma were less cytotoxic and expressed less IFN-γ than NK cells from healthy donors. NK cells from severe asthmatics exhibited an exhausted phenotype, with an increased expression of the checkpoint molecule Tim-3.Together, our findings indicate that the activation of NK cells from patients with severe asthma may be insufficient during some but not all respiratory infections. The exhausted phenotype may participate in NK cell impairment and aggravation of viral-induced asthma exacerbation in these patients.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S758-S758
Author(s):  
Aviva Szigeti ◽  
Margaret Hammerschlag ◽  
Diana Weaver ◽  
Tamar Smith-Norowitz ◽  
Stephan Kohlhoff

Abstract Background Chlamydia pneumoniae (Cpn) is unique in its ability to cause chronic infections, potentially triggering asthma exacerbations as well as subsequent asthma development. Th1-mediated immunity and IFN-γ are critical for clearing chlamydial infections. Persistent or recent Cpn infection may be identified in vitro by detecting T-helper cytokine IFN-γ produced by peripheral blood mononuclear cells (PBMC) stimulated by Cpn. Inhaled corticosteroids (ICS) may have an inhibitory effect on IFN-γ. Prior studies have shown increased Th2 responses upon in vitro Cpn stimulation with increased age. Our aim was to determine whether age and inhaled corticosteroid (ICS) use affect Cpn-induced PBMC produced IFN-γ levels. Methods Pediatric and adult subjects with (n = 23) and without (n = 10) asthma were enrolled. PBMC obtained from all subjects were stimulated with Cpn (MOI = 0.1 x48h) in vitro. IFN-γ levels in culture supernatants were determined by ELISA and reported as pg/mL. Nasopharyngeal (NP) swabs were tested for Cpn using Real-Time PCR. Statistical analysis for continuous variables was performed using the Mann–Whitney U test. Results None of the subjects were positive for Cpn by PCR on NP swab. Levels of IFN-γ produced by PBMC stimulated by Cpn were similar between asthmatic vs. control subjects (41.7 vs. 68.8, respectively; P = 0.72) and between pediatric and adult subjects with asthma (IFN-γ 54 vs. 20.1 respectively, P = 0.95). Pediatric subjects with asthma who received ICS had lower IFN-γ levels than those who did not (median IFN-γ 25.5 vs. 209; P = 0.003). Conclusion Our finding of lower IFN-γ levels among asthma patients on ICS compared with those not on ICS suggests that ICS use may dampen the systemic inflammatory response. While we did not find a statistically significant difference between pediatric and adult age groups in this pilot study, there was a trend to higher Cpn-induced IFN-γ levels among younger pediatric subjects. Future prospective studies should further define predictors of diminished IFN-γ responses in patients with asthma. Disclosures All authors: No reported disclosures.


2018 ◽  
Vol 20 (6) ◽  
pp. 913-920
Author(s):  
M. V. Antonyuk ◽  
T. A. Gvozdenko ◽  
T. P. Novgorodtseva ◽  
T. I. Vitkina ◽  
B. I. Geltser ◽  
...  

Combination of bronchial asthma (BA) and obesity is a difficult-to-control phenotype. Studies of inflammatory process with respect to severity of the disease are important for understanding the potential influence of obesity on the BA clinical course. The objective of this study was to determine cytokine profile in patients with mild BA combined with obesity. The study involved fifty-three patients with partially controlled mild BA. The patients were recruited as volunteers and signed an informed consent. The first observation group consisted of 27 asthma patients with normal body weight, the second observation group consisted of 26 patients with BA combined with obesity. A control group included 25 healthy volunteers. All the patients underwent clinical and laboratory examination in accordance with clinical standards for BA and obesity. The levels of TNFα, IL-2, IL-4, IL-6, IL-10 were evaluated in blood serum by means of flow cytometry. The ratios of proand anti-inflammatory cytokines (TNFα/IL-4, TNFα/IL-10, IL-6/IL-4, IL-6/IL-10) were calculated. Asthma patients with obesity (the 2nd group) had elevated levels of IL-2 over control group and group 1, by 38% and 44% respectively(p < 0.05). The concentration of proinflammatory cytokines TNFα and IL-6 was significanty increased in the both patient groups. Mean TNFα level was increased 2.5 times (p < 0.05), and IL-6 levels were increased by 30% (p < 0.05) in the 1st group as compared to the controls. TNFα and IL-6 concentrations showed a 3-fold increase over control values (p < 0.05) in the 2nd group. The level of antiinflammatory cytokine IL-4 was increased in patients with BA, independently of body mass. It should be noted that the concentration of this cytokine in obese patients was higher by 29% than in patients with normal body weight. IL-10 levels in patients from the 2nd group were reduced more than 2 times than in the 1st group. The patients of the 1st group showed a decrease in the IL-6/IL-10 index, in comparison with control parameters, thus indicative of an imbalance due to the elevation of the anti-inflammatory IL-10 cytokine. Among BA patients with obesity (group 2) the TNFα/IL-10 and IL-6/IL-10 indexes were higher than those of the control group (2.3- and 5.5-fold, respectively) and the group 1 (2.6- and 2.5-fold, respectively). Dynamics of these indexes confirms the systemic nature of inflammation and a predominance of non-atopic  inflammation in asthma patients with obesity. Thus, features of the cytokine profile in BA with obesity consist of a significant increase in pro-inflammatory IL-2, IL-6, TNFα cytokines, and a relative decrease in anti-inflammatory IL- 10 cytokine. The development of BA with obesity, even in mild-severity BA, is accompanied by development of a cytokine disbalance, which is typical for a mixed-type inflammation, with a prevalence of neutrophil inflammation. 


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