CD4+CD25+Treg细胞与支气管哮喘

CD4+ CD25+ Treg细胞的主要作用表现为免疫无能性和免疫抑制性,是外周免疫耐受形成机制的主要组成部分.其主要作用机制为分泌抑制性细胞因子(IL-10和TGF-β)、表达细胞表面分子(CTLA-4、GITR等)及Foxp3等.支气管哮喘患者外周血CD4+ CD25+ Treg功能及数量存在异常,这可能是支气管哮...     

CD4＋CD25＋Treg细胞与支气管哮喘

CD4＋CD25＋Treg细胞的主要作用表现为免疫无能性和免疫抑制性,是外周免疫耐受形成机制的主要组成部分。其主要作用机制为分泌抑制性细胞因子（IL-10和TGF-β）、表达细胞表面分子（CTLA-4、GITR等）及Foxp3等。支气管哮喘患者外周血CD4＋CD25＋Treg功能及数量存在异常,这可能是支气管哮喘发病机制之一。糖皮质激素可以通过影响CD4＋CD25＋Treg的状态起到抑制支气管哮喘气道炎症的作用。     

Sputum CD34+IL-5Ralpha+ cells increase after allergen: evidence for in situ eosinophilopoiesis

Eosinophil lineage-committed progenitors increase in the bone marrow of subjects with asthma developing allergen-induced airway hyperresponsiveness and eosinophilia. Also, higher numbers of circulating eosinophil/basophil cfu have been demonstrated 24 hours after allergen inhalation and in bronchial and nasal biopsies of allergic individuals. These cells may undergo in situ eosinophilopoiesis, suggesting that after allergen inhalation, progenitor cells traffic from the bone marrow to the airways, providing an ongoing source of effector cells. To examine this possibility, CD34(+) and CD34(+)IL-5Ralpha(+) cells were measured in induced sputum from allergic subjects with asthma at baseline and at 7 and 24 hours after allergen and diluent inhalation, using flow cytometry. Isolated early responders (n = 9) were contrasted to dual responders (n = 9), who develop allergen-induced sputum and blood eosinophilia and airway hyperresponsiveness, and to normal control subjects. At baseline, there were significantly fewer sputum eosinophils and CD34(+) cells in normal control subjects compared with subjects with asthma. Sputum CD34(+) cells increased at 7 hours after allergen inhalation in both groups of subjects with asthma, which was sustained at 24 hours in the dual responder group only, associated with sustained increases in sputum CD34(+)IL-5Ralpha(+) cells, eosinophils, and interleukin-5. These results indicate that eosinophil progenitors can migrate to the airways and may differentiate toward an eosinophilic phenotype.     

CD+4CD+25 T淋巴细胞对支气管哮喘小鼠气道炎症的影响及作用机制

目的探讨CD+4 CD+25 T淋巴细胞(Treg细胞)对支气管哮喘(简称哮喘)小鼠气道炎症的影响及作用机制.方法 60只小鼠按随机数字表法分为3组,每组20只.哮喘组(A组)小鼠于第1、13天以鸡卵白蛋白(OVA)0.1 ml腹腔注射致敏,第21～29天雾化吸入2% OVA生理盐水溶液10 ml激发 30 min后建立小鼠哮喘模型.生理盐水对照组(B组)以生理盐水10 ml替代OVA处理.去除T淋巴细胞哮喘组(C组)去除小鼠体内CD+25 T淋巴细胞后再按A组方法复制小鼠哮喘模型(用药剂量和方法同A组).分离A、B、C 3组小鼠脾脏淋巴细胞,用流式细胞仪(FACS)检测Treg细胞数量,计算其占CD+4 T淋巴细胞的百分比;分离CD+4 T淋巴细胞,用逆转录-聚合酶链反应(RT-PCR)法检测白细胞介素10(IL-10)、转化生长因子β1(TGF-β1)和细胞毒性T淋巴细胞抗原4 mRNA(CTLA-4 mRNA)的表达;同时对肺组织行苏木精-伊红 (HE)染色,观察小鼠肺组织的炎症改变. 结果经过OVA反复激发,A组小鼠脾脏Treg细胞占CD+4 T淋巴细胞的百分比为(3.10±0.03)%,B组为(9.60±0.04)%,A、B两组间及C组分别与A、B组比较差异均有统计学意义(P均<0.01); IL-10、TGF-β1和CTLA-4 mRNA的表达A组分别为0.250±0.040、0.29±0.03、0.28±0.06, B组分别为0.480±0.080、0.47±0.05、0.50±0.03、C组分别为0.080±0.020、0.11±0.04、0.12±0.05,A、B两组及C组分别与A、B组比较差异均有统计学意义(P均<0.01).与B组比较,A组肺部以嗜酸粒细胞浸润为主要表现的炎症改变明显增强,C组则较A、B组显著增强.结论 Treg细胞的数量减少和(或)功能障碍可能是哮喘气道炎症发生发展的重要机制.     

Increased interleukin-4, interleukin-5, and interferon-gamma in airway CD4+ and CD8+ T cells in atopic asthma

Increased Th2 cytokine production in asthma is widely accepted, but excess production by asthmatic human airway CD4(+) T cells has not been demonstrated, nor has a relationship with disease severity. The importance of airway CD8(+) T cell type 1 and type 2 cytokine production in asthma is unknown. We investigated frequencies of IFN-gamma, interleukin (IL)-4 and IL-5 producing CD4(+) and CD8(+) blood and sputum T cells from normal subjects and subjects with asthma and compared between cell subsets, subject groups, and body compartments with and without in vitro stimulation and investigated relationships between cytokine production and asthma severity. Production of IL-4, IL-5, and IFN-gamma by unstimulated sputum CD4(+) and CD8(+) T cells was increased in subjects with asthma and related to disease severity, more for CD8(+) than for CD4(+) T cells. Frequencies of sputum CD8(+) T cells producing type 1 and type 2 cytokines were similar to those of CD4(+) T cells. In vitro stimulation polarized peripheral blood cytokine production toward IFN-gamma production, significantly more in subjects with asthma than in normal subjects. These data demonstrate increased type 1 and 2 cytokine production in CD4(+) and CD8(+) T cells in sputum and relate production to disease severity. Findings in blood did not reflect those in airways.     

Potential Mechanisms of Improvement of Airway Hyperresponsiveness by Inhaled Corticosteroid Therapy in Asthmatic Patients

Objective. Recent clinical trials with administration of IL-5 antibodies to asthmatic patients have revealed reduction of eosinophilia but unaltered airway hyperresponsiveness (AHR). In contrast, inhaled corticosteroid (ICS) therapy eliminates both eosinophilia and AHR. This study was designed to examine the mechanisms by which ICS improves airway hyperresponsiveness in asthmatic patients.

Methods. Clinical variables of asthma involving vascular permeability and IL-5 levels were examined in 23 asthmatic patients and 11 normal control subjects. After the first sputum induction, inhaled beclomethasone dipropionate (BDP 800 μg/day) was administered to asthmatic patients for 8 weeks, and sputum induction was repeated.

Results. IL-5 levels in induced sputum and airway vascular permeability index were significantly higher in asthmatic patients. IL-5 was positively correlated with percentage of eosinophils in induced sputum, and negatively correlated with FEV1, but not correlated with PC₂₀ methacholine. After BDP therapy, eosinophils, ECP, and IL-5 levels were significantly decreased to the same levels as in normal subjects. Conversely, PC₂₀ methacholine and airway vascular permeability did not improve to the same levels as in normal subjects. Increase in PC₂₀ methacholine from before to after BDP therapy was significantly correlated with decrease in airway permeability index, but not with decrease in IL-5 level.

Conclusion. Our results suggest a clear dissociation between IL-5 and AHR. ICS therapy improves AHR at least in part through decrease in airway vascular permeability.     

Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma

IgE plays an important role in allergic asthma. We hypothesized that reducing IgE in the airway mucosa would reduce airway inflammation. Forty-five patients with mild to moderate persistent asthma with sputum eosinophilia of 2% or more were treated with humanized monoclonal antibody against IgE (omalizumab) (n = 22) or placebo (n = 23) for 16 weeks. Outcomes included inflammatory cells in induced sputum and bronchial biopsies, and methacholine responsiveness. Treatment with omalizumab resulted in marked reduction of serum IgE and a reduction of IgE+ cells in the airway mucosa. The mean percentage sputum eosinophil count decreased significantly (p < 0.001) from 6.6 to 1.7% in the omalizumab group, a reduction significantly (p = 0.05) greater than with placebo (8.5 to 7.0%). This was associated with a significant reduction in tissue eosinophils; cells positive for the high-affinity Fc receptor for IgE; CD3+, CD4+, and CD8+ T lymphocytes; B lymphocytes; and cells staining for interleukin-4, but not with improvement in airway hyperresponsiveness to methacholine. This study shows antiinflammatory effects of omalizumab treatment and provides clues for mechanisms whereby omalizumab reduces asthma exacerbations and other asthma outcomes in more severe asthma. The lack of effect of omalizumab on methacholine responsiveness suggests that IgE or eosinophils may not be causally linked to airway hyperresponsiveness to methacholine in mild to moderate asthma.     

Role for CTLA-4 but not CD25+ T cells during Schistosoma mansoni infection of mice

Schistosoma mansoni infection of mice increases the frequency of cells that are CD4+ CD25+ in the acute (4 and 8 weeks) and chronic (16 week) stages of infection. Depletion of > 85% of CD25+ cells in the acute or chronic stages of schistosome infection caused no overt changes in morbidity or immunological responses. The absence of effect in mice with CD25+ cells depleted may be due to the preferential expression of IL-4 and IL-10, two cytokines that are protective in schistosome infection, on CD25- CD4+ cells. We also assessed infection-induced changes of other regulatory markers, GITR, CD103 and CTLA-4 on CD4+ cells. We identified a marked expansion of CTLA-4+ population on CD25- CD4+ cells in acute and chronic infection. Blocking of CTLA-4 during acute, but not chronic infection, caused significant weight loss and altered the type 2 cytokine response of mice, with increased IL-4 and IL-5 production associated with significantly more Th2 cells and eosinophils in the liver granuloma. This study illustrates the complexity of regulation of T cells in schistosome infection and highlights a specific role for CTLA-4+, but not CD25+ cells, in the regulation of Th2 responses in helminth infection.     

地塞米松对哮喘小鼠CD4+CD25+调节性T细胞及IL-4、IL-10水平的影响

目的 探讨地塞米松对哮喘小鼠CD4+ CD25+调节性T细胞及IL-4、IL-10水平的影响.方法 30只雄性BALB/c小鼠随机分为三组:正常对照组、哮喘组和地塞米松组.利用卵清白蛋白腹腔注射和雾化吸入制备哮喘模型;通过流式细胞仪检测各组小鼠脾脏单个核细胞CD4+ CD25+调节性T细胞占CD4+T细胞的百分比;使用免疫组织化学方法分析各组IL-4在小鼠肺组织中的表达情况;用酶联免疫吸附试验检测各组小鼠血清IL-10的水平.结果 哮喘组脾脏单个核细胞CD4+CD25+调节性T细胞百分比及IL-10的表达水平较正常对照组和地塞米松组降低(P＜0.05),哮喘组IL-4水平较正常对照组和地塞米松组增高(P＜0.05).结论 地塞米松的抗炎作用可能通过上调CD4+ CD25+调节性T细胞、调节性T细胞亚群失衡的途径来实现.     

Decreased CTLA4+ and Foxp3+ CD25highCD4+ Cells in Induced Sputum from Patients with Mild Atopic Asthma

BackgroundDetails of the comparisons between airway and peripheral blood regulatory T cells (Tregs) in patients with atopic asthma are still unclear. The objective of this study is to investigate the profiles of both airway and circulating Tregs in atopic asthma.MethodsWe measured the numbers of Tregs and eosinophils in induced sputum and peripheral blood in 28 patients with mild atopic asthma and compared these with numbers in 18 healthy controls. The frequency (%) of Tregs (surface CTLA4⁺, intracellular Foxp3⁺, and CTLA4⁺Foxp3⁺ on CD25^highCD4⁺ T cells) in sputum and blood was determined by intracellular 5-color flow cytometry. We also correlated the numbers with the level of airway hyperresponsiveness (AHR) in asthmatics.ResultsThe mean frequencies of cells expressing CTLA4⁺ (19.4 ± 2.1%, p = 0.075), Foxp3⁺ (16.4 ± 3.3%, p = 0.001), and CTLA4⁺Foxp3⁺ (7.0 ± 1.1%, p = 0.008) in induced sputum from asthmatics were significantly lower than controls (27.2 ± 3.7%, 37.4 ± 4.7%, and 18.2 ± 3.6%, respectively), whereas in peripheral blood, there was no inter-group difference in the frequencies of cells expressing CTLA4⁺ (7.1 ± 1.5% vs 5.7 ± 1.7%, p > 0.05), Foxp3⁺ (35.7 ± 3.2% vs 21.1 ± 3.9%, p > 0.05), and CTLA4⁺Foxp3⁺ (6.6 ± 1.5% vs 4.2 ± 1.0%, p > 0.05). Moreover, the frequency of CD25^highCD4⁺ cells expressing CTLA4⁺, but not Foxp3⁺, in induced sputum was associated with AHR (r = 0.60, p = 0.009) and airway eosinophilic inflammation (r = ? 0.60, p = 0.008) in asthmatics.ConclusionsAirway, but not circulating, Tregs are decreased in mild atopic asthmatics, and are negatively correlated to an increase of airway eosinophilic inflammation and AHR.     

Increased expression of the chemoattractant cytokines eotaxin, monocyte chemotactic protein-4, and interleukin-16 in induced sputum in asthmatic patients

BACKGROUND: Induced sputum from asthmatic patients has been recently used to assess inflammatory cells. We have previously reported an increased expression of Th-2-type cytokines in induced sputum of asthmatic patients. C-C chemokines, particularly eotaxin and monocyte chemotactic protein (MCP)-4, are associated with eosinophilic infiltration. Interleukin (IL)-16 is associated with chemotactic activity for CD4+ cells. Chemokine expression in BAL and bronchial biopsy specimens has been demonstrated in asthmatic airways, but not in induced sputum. METHODS: We examined whether eotaxin, MCP-4, and IL-16 expression could be detected in induced sputum of asthmatic patients (n = 10), and whether the expression was increased compared to normal control subjects (n = 9). Eotaxin, MCP-4, and IL-16 immunoreactivity were determined by immunocytochemistry. In addition, inflammatory cells were investigated using markers for T cells (CD3), eosinophils (major basic protein [MBP]), macrophages (CD68), neutrophils (elastase), and epithelial cells (cytokeratin). RESULTS: Our results showed that there was a significant difference in the percentages of MBP-positive and epithelial cells between asthmatic patients and normal control subjects (p < 0.05). However, there was no difference between these two groups in the percentage of CD3-, elastase-, and CD68-positive cells. Immunoreactivity for eotaxin, MCP-4, and IL-16 was expressed in the induced sputum of all asthmatic patients, and expression of these chemotactic cytokines was significantly greater than in control subjects (p < 0.001, p < 0.005, and p < 0.001, respectively). CONCLUSIONS: This study showed that induced sputum could be used to detect chemokines in patients with bronchial asthma, and that the upregulation of chemotactic cytokines in the airways can be seen using noninvasive techniques.     

Increased IL-4- and IL-17-producing CD8+ cells are related to decreased CD39+CD4+Foxp3+ cells in allergic asthma

Objective: In allergic asthma, regulatory T cell (Treg) number and function are decreased. Antigen-primed CD8⁺ T cells play an indispensable role in the full development of airway inflammation and airway hyper-responsiveness (AHR) occurring in asthma. In this study, we investigated the relationship between subpopulations of CD8⁺ T cells and CD39⁺ Tregs. Methods: Female C57BL/6 mice were used to develop the model of allergic asthma. Experimental mice were immunized with ovalbumin (OVA) by intra-peritoneal (i.p) injection and then challenged with OVA by intra-tracheal administration. Control mice were immunized with vehicle by i.p injection and challenged with OVA. Airway inflammation was determined by histology and AHR was measured by an invasive method. Levels of interferon (IFN)-γ, IL-4, and IL-17 in bronchoalveolar lavage fluid (BALF) were determined by enzyme-linked immunosorbent assay. The frequencies of CD8⁺IFN-γ⁺ cells (Tc1), CD8⁺IL-4⁺ cells (Tc2), CD8⁺IL-17⁺cells (Tc17), and CD39⁺Tregs were measured by flow cytometry. The correlation between CD39⁺Tregs and Tc subsets was analyzed by Pearson’s test. Results: Experimental mice displayed phenotypes of allergic asthma, including inflammatory cell infiltration into the lungs, goblet cell hyperplasia, increased airway resistance, and increased IL-4 and IL-17 in BALF. Compared to control mice, experimental mice displayed lower CD39⁺Tregs and Tc1 but higher Tc2 and Tc17. There was a negative correlation between CD39⁺Tregs and Tc2 or Tc17. Conclusion: In allergic asthma, increased Tc2 and Tc17 are possibly related to insufficient CD39⁺Tregs.     

Potential Mechanisms of Improvement of Airway Hyperresponsiveness by Inhaled Corticosteroid Therapy in Asthmatic Patients

Objective. Recent clinical trials with administration of IL-5 antibodies to asthmatic patients have revealed reduction of eosinophilia but unaltered airway hyperresponsiveness (AHR). In contrast, inhaled corticosteroid (ICS) therapy eliminates both eosinophilia and AHR. This study was designed to examine the mechanisms by which ICS improves airway hyperresponsiveness in asthmatic patients.

Methods. Clinical variables of asthma involving vascular permeability and IL-5 levels were examined in 23 asthmatic patients and 11 normal control subjects. After the first sputum induction, inhaled beclomethasone dipropionate (BDP 800 μg/day) was administered to asthmatic patients for 8 weeks, and sputum induction was repeated.

Results. IL-5 levels in induced sputum and airway vascular permeability index were significantly higher in asthmatic patients. IL-5 was positively correlated with percentage of eosinophils in induced sputum, and negatively correlated with FEV1, but not correlated with PC₂₀ methacholine. After BDP therapy, eosinophils, ECP, and IL-5 levels were significantly decreased to the same levels as in normal subjects. Conversely, PC₂₀ methacholine and airway vascular permeability did not improve to the same levels as in normal subjects. Increase in PC₂₀ methacholine from before to after BDP therapy was significantly correlated with decrease in airway permeability index, but not with decrease in IL-5 level.

Conclusion. Our results suggest a clear dissociation between IL-5 and AHR. ICS therapy improves AHR at least in part through decrease in airway vascular permeability.     

Different roles of interleukin-10 in onset and resolution of asthmatic responses in allergen-challenged mice

OBJECTIVE: Although interleukin (IL)-10 is an immunoregulatory cytokine produced by various cells including T cells, its precise role in asthma remains uncertain. The aim of this study was to investigate the role of IL-10 in experimental asthma using ovalbumin (OVA)-sensitized mice. METHODOLOGY: Mice were challenged with OVA aerosol, and airway responsiveness and inflammation were measured. OVA-specific IL-10-producing CD4+ T cells were counted from lung cells collected by enzymatic digestion and stimulated ex vivo with OVA. The effects of an anti-IL-10 antibody on airway responsiveness and inflammation were also evaluated. RESULTS: The OVA challenge caused airway hyperresponsiveness and eosinophilic inflammation. A significant increase in IL-10-producing CD4+ T cells was observed, mainly in the CD45RB(low) subset, for several days after the OVA challenge. Anti-IL-10 antibody treatment before the OVA challenge did not affect eosinophilic inflammation but significantly inhibited airway hyperresponsiveness 24 h after the OVA challenge. However, anti-IL-10 antibody treatment just before the last OVA challenge significantly attenuated the resolution of eosinophilic inflammation without affecting airway responsiveness 2 weeks after the OVA challenge. CONCLUSIONS: Intrinsic IL-10 may have a distinct role in the early and late phases of asthmatic responses. In the early phase, IL-10 induces airway hyperresponsiveness, while in the late phase IL-10 contributes to the resolution of eosinophilic inflammation.     

Different IL-5 and IFN-γ Production from Peripheral Blood T-Cell Subsets in Atopic and Nonatopic Asthmatic Children

Defective Th1 and enhanced Th2-type cytokine responses have been implicated in the development of atopic disease. However, the immunopathology of nonatopic asthma, especially in children, remains unclear, and there have been few studies to compare the cytokine profile in peripheral blood T-cell subsets between atopic and nonatopic asthmatic children. To document whether atopic asthmatic children have a cytokine imbalance and to compare the cytokine profile between atopic and nonatopic asthmatic children, we investigated the interleukin (IL)-5-producing and interferon (IFN)-γ-producing T-cell subsets from peripheral blood mononuclear cells (PBMC). The percentages of IFN-γ-producing CD4⁺ and CD8⁺ T cells from atopic asthmatic children were decreased, but those in nonatopic asthmatic children were not decreased. In both groups of asthmatic children, the percentages of IFN-γ-producing CD4⁺ T cells were inversely correlated with the peripheral blood eosinophils and had a significant correlation with airway responsiveness (PC₂₀). Thus, we found that the mechanism underlying allergic inflammation of nonatopic asthma is not simple a Th1/Th2 cytokine imbalance. Considering the inverse relationship between IFN-γ-producing CD4⁺ T cells and eosinophilia or airway hyperresponsiveness, IFN-γ from CD4⁺ T cells may play an important role in allergic inflammation and airway hyperresponsiveness in asthmatic children.     

CD4＋CD25＋调节性T细胞与支气管哮喘的研究进展

支气管哮喘（简称哮喘）是一种气道慢性过敏反应炎症性疾病,表现为反复发作性喘息、胸闷和咳嗽。近年来CD4＋CD25＋调节性T细胞在哮喘发病机制中的作用及其在哮喘治疗中的应用越来越受到人们的关注。现将CD4＋CD25＋调节性T细胞与哮喘的最新研究进展作一综述。     

Apoptotic eosinophils in sputum from asthmatic patients correlate negatively with levels of IL-5 and eotaxin

BACKGROUND: Eosinophilic inflammation of the airways is a key characteristic of asthma. A defect in eosinophil apoptosis might contribute to the chronic tissue eosinophilia associated with asthma. OBJECTIVE: Our purpose was to examine whether the occurrence of apoptotic eosinophils in induced sputum from asthmatic patients correlate with interleukin (IL)-5 and eotaxin. METHODS: Thirty stable and 30 exacerbated asthmatic patients were recruited. Twenty healthy subjects were enrolled as a control group. Induced sputum was obtained from asthmatic patients and from control subjects. The number of apoptotic eosinophils in sputum was assessed by flow cytometry. In sputum supernatant, eosinophil cationic protein (ECP) was measured by sensitive radioimmunoassay, and IL-5 and eotaxin by sandwich enzyme linked immunosorbant assay. RESULTS: Levels of eosinophils, apoptotic eosinophils, IL-5, ECP and eotaxin from asthmatic patients were higher than those from healthy subjects. Thirty exacerbated asthmatics showed higher proportions of eosinophils (median 29.3%, range 13.4%-40.9%), more detectable levels of IL-5 (50.44, 32.99-67.01 pg/ml) and eotaxin (644.6, 197.4-937.7 pg/ml) in their sputum than the patients with stable asthma (P<0.05). There were significant inverse correlations between the levels of sputum IL-5 and the proportion of sputum eosinophil apoptosis in patients with exacerbated and stable asthma (r=-0.85 and -0.79, P<0.01 and P<0.05, respectively). Also inverse correlations were found between the levels of eotaxin and the proportion of sputum eosinophil apoptosis in exacerbated (r=-0.85, P<0.01), or stable asthma (r=-0.69, P<0.05). Additional positive correlations between the levels of sputum IL-5 and eotaxin in either exacerbatated (r=0.93, P<0.01) or stable asthma (r=0.82, P<0.05) were observed. CONCLUSIONS: Apoptosis of eosinophils might be suppressed by proinflammatory cytokines and chemokines such as IL-5 and eotaxin leading to their accumulation in the lung. Stimulation of eosinophils in airway with IL-5 and eotaxin may play a crucial role in allergic inflammation.     

Magnesium Affects the Cytokine Secretion of CD4+ T Lymphocytes in Acute Asthma

Introduction. Magnesium (Mg) administration has been shown to promote bronchodilation and to improve lung function in asthma. It also plays an additional role in modulating the immune responses. This study was initiated to explore if Mg supplementation could affect the secretion of cytokines in acute asthmatic CD4⁺ T cells. Methods. Total serum Mg concentrations of the acute asthmatic patients and healthy controls were determined. CD4⁺ T cells were isolated from the blood of the acute asthmatic patients. They were cultured in various concentrations of Mg-supplemented (0.8, 5, 10, 15, and 20 mmol/l) medium. Cytokine (IL-5, IL-13, and IFN-γ) levels were determined by Enzyme-Linked Immunosorbnent Assay (ELISA). Results. Serum Mg concentration was lower in the acute asthmatic patients than that in the healthy controls (p < .05). The secretion of IL-5 and IL-13 was decreased, while the acute asthmatic CD4⁺ T cells were cultured in 10 and 15 mmol/l Mg-supplemented medium, respectively, as compared to the 0.8 mmol/l Mg group (p < .05). The secretion of IFN-γ increased in the 10 mmol/l Mg group (p < .05). Conclusion. Mg supplementation was able to modulate the immune responses of acute asthmatic CD4⁺ T cells and decrease the secretion of type 2 CD4⁺ T lymphocytes cytokines.     

哮喘患者辅助T细胞活化与白细胞介素5释放

目的 了解过敏状态和哮喘状态下辅助（ＣＤ４＾＋）Ｔ细胞活化及白细胞介素５（ＩＬ－５）释放的原因和作用。方法 对过敏性哮喘组１２例（ＡＡ）、非过敏性哮喘组１０例（ＮＡＡ）、过敏性非哮喘组９例（ＡＮ）及正常对照组１０名（Ｎ）在有无抗原刺激下进行支气管肺泡灌洗液（ＢＡＬＦ）细胞及周围血单个核细胞（ＰＢＭＣ）培养，比较组内和组间ＣＤ４＾＋Ｔ细胞活化（标志物ＣＤ２５＾＋）与ＩＬ－５释放水平。结果 ＰＢＭＣ在     

Smoking Affects Eotaxin Levels in Asthma Patients

Background. Chronic airway inflammation is most important pathological finding in asthma. Cigarette smoking may modify type of inflammation as well as may influence disease severity and response to the treatment. Objective. Thus the aim of this study was to investigate whether cigarette smoking may have an influence on the levels of eotaxin-1, eotaxin-2, eotaxin-3 and IL-5 in patients with stable mild/moderate asthma. Methods. 45 steroid naive asthmatics (mean age: 55.2 ± 2.2 yrs) and 23 “healthy” smokers and non-smokers control subjects (mean age: 54.4 ± 9.7 yrs) were investigated. Asthmatics were divided into two subgroups according to their smoking histories: asthmatic smokers (n = 19) who currently smoke and have a history of > 10 pack-years and asthmatic never-smokers (n = 26). BAL and induced sputum were performed. Cytospins of induced sputum and BAL were stained with May-Grünwald-Giemsa for differential cell counts. Eotaxin-1, eotaxin-2, eotaxin-3 and IL-5 concentrations in serum, sputum and BAL supernatant was measured using a commercial ELISA kit. Results. In sputum supernatant from asthma smokers was significantly higher concentration of eotaxin-1 than in non-smokers asthmatics (203.4 ± 10.0 vs. 140.2 ± 9.5 respectively, p < 0.05). In non-smokers asthma patients levels of BAL eotaxin-1 strongly related to percent and absolute numbers of BAL eosinophils and neutrophils (Rs = 0.737 and Rs = 0.514 respectively, p < 0.05). The number and percent of sputum neutrophils and eosinophils, obtained from smokers asthmatics, significantly correlated with eotaxin-2 concentration in sputum supernatant (Rs = 0.58 and Rs = 0.75 respectively, p < 0.05). IL-5 levels in the serum and sputum from asthmatic never-smokers were significantly higher than they were from asthmatic smokers and “healthy” smokers. Asthmatic never-smokers showed a significantly higher amount of IL-5 in serum and sputum than the asthmatic smokers showed. Conclusions. This study showed the elevated levels of sputum eotaxin-1 as well as serum, sputum and BAL eotaxin-2 in asthmatic smokers without a significant increase of eosinophils compared to asthmatic never-smokers. The eotaxin concentrations were related not only with number of eosinophils but also with the number of neutrophils in all the studied tissue compartments. The data herein permits a suggestion that smoking may influence change in asthmatic airway inflammation by stimulating the production of eotaxins.