Cytokine responses during exacerbation compared with stable phase in asthmatic children (original) (raw)
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Inflammation, 2014
The role of adaptive immune system in regulation of asthmatic responses remains elusive. Here, we performed a comprehensive time-course analysis of mutual relationships between development of asthmatic response following allergen challenge and changes in several CD4+ T cell subsets which we characterized as either releasing interleukin-10 (CD4+CD25−CD127− and CD4+CD25+CD127+ T cells) or responding to IL-10 (CD4+ T cell subsets expressing CD210). Patients that developed asthmatic reaction were described as responders (R) whereas the others were named non-responders (NR). In R, in contrast to NR, at 6 h, we demonstrated significant expansion of CD4+CD25−CD127− T cells which was followed by drop to baseline values at 24 h. In contrast, in R, we observed decrease in numbers of CD4+CD25+CD127+ and CD4+CD25−CD127+ T cells at 24 h. Interestingly, at baseline, despite comparable IL-10 levels, R presented with lower levels of all CD4+ T cell subsets expressing CD210. In R, the numbers of CD4+CD210+ T cell subsets were further decreased following bronchial challenge which was paralleled by decrease in IL-10 serum levels. Altogether, our data suggest that dynamic interactions between IL-10-producing and IL-10-responding CD4+ T cells could contribute to pathogenesis of asthmatic responses in atopic individuals.
Canadian respiratory journal : journal of the Canadian Thoracic Society
Interleukin (IL)-10 is a pleiotropic cytokine released from various cells, including T cells. Although IL-10 is suggested to inhibit allergic responses, its role in asthma remains uncertain. The purpose of the present study was to compare the profile of IL-10 in circulating T cells from stable atopic asthmatics, atopic nonasthmatics and healthy controls. Peripheral blood mononuclear cells were isolated, stained with anti-CD3 and CD4/CD8 antibodies, and then processed for intracellular IL-10 detection by flow cytometry. A kinetic study in healthy controls showed that stimulation with phorbol 12-myristate 13-acetate and ionomycin significantly increased the frequencies of IL-10-producing CD3+, CD4+ and CD8+ cells. Without stimulation, the frequencies of IL-10-producing CD3+, CD4+ and CD8+cells were significantly higher in asthmatics than in healthy controls, while a similar trend was observed in atopic nonasthmatics. Stimulation for 24 h significantly increased IL-10-producing CD3+, C...
American Journal of Respiratory and Critical Care Medicine, 2005
Increased Th2 cytokine production in asthma is widely accepted, but excess production by asthmatic human airway CD4 ϩ T cells has not been demonstrated, nor has a relationship with disease severity. The importance of airway CD8 ϩ T cell type 1 and type 2 cytokine production in asthma is unknown. We investigated frequencies of IFN-␥, interleukin (IL)-4 and IL-5 producing CD4 ϩ and CD8 ϩ 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-␥ by unstimulated sputum CD4 ϩ and CD8 ϩ T cells was increased in subjects with asthma and related to disease severity, more for CD8 ϩ than for CD4 ϩ T cells. Frequencies of sputum CD8 ϩ T cells producing type 1 and type 2 cytokines were similar to those of CD4 ϩ T cells. In vitro stimulation polarized peripheral blood cytokine production toward IFN-␥ production, significantly more in subjects with asthma than in normal subjects. These data demonstrate increased type 1 and 2 cytokine production in CD4 ϩ and CD8 ϩ T cells in sputum and relate production to disease severity. Findings in blood did not reflect those in airways.
Allergy, 2010
Background: Although mild to moderate asthma is known to be Th2 driven, cytokines produced in refractory asthma might not fit the classical Th2 pattern. Methods: The aim of our study was to assess the cytokine production by sputum and blood cells from 15 refractory asthmatics (American Thoracic Society Criteria) compared to 15 mild untreated and 17 moderate treated asthmatics and 22 healthy subjects. Spontaneous production of interleukin (IL)-4, IL-6, IL-10, interferon-c, and tumor necrosis factor a was measured by immunotrapping after 24 h sputum or blood cell culture. Results: Moderate and refractory asthmatics were both characterized by a lower production of IL-6 from their airway cells compared to healthy subjects. However, the difference was no longer significant when expressing the results per gram of sputum. No significant difference between the three groups was found regarding other cytokines. As for cytokine production from blood, the three groups of asthmatics exhibited raised production of IL-4 when compared to healthy subjects, and this was true when results were expressed per blood volume or after normalization for total leukocyte cell count. Moderate asthmatics exhibited greater production of IL-10 when compared to refractory asthmatics and healthy subjects when results were normalized for total leukocyte cell count. Conclusions: Sputum cells from moderate and refractory asthmatics release less IL-6. While the systemic overproduction of IL-4 was observed through the all spectrum of asthma severity, moderate asthmatics exhibited greater systemic IL-10 production compared to refractory asthmatics.
Pediatric Asthma, Allergy & Immunology, 1996
Background: The pathogenesis of asthma involves hyperreactivity and chronic inflammation of airways in which CD4+ T cells play a major role. In atopic asthmatics, Thl responses due to interferon-gamma (IFN-y) are depressed, and Th2 responses due to interleukins (IL-4, IL-10) are predominant. It is not clear if cytokine secretion patterns change with clinical improvement during immunotherapy. Objectives: Monitoring IFN-y and IL-10 may be very useful in evaluating the effectiveness and response to allergen immunotherapy and in developing new therapeutic interventions with specific cytokine antagonists or peptides. Materials and Methods: Peripheral blood mononuclear cells were obtained from healthy nonasthmatic controls (N = 5) and from atopic asthmatic patients (N = 5) prior to immunotherapy and at 3 and 6 months after initiation of immunotherapy to monitor cytokine secretion (IFN-y, IL-10) in unstimulated and grass and ragweed allergen-specific stimulated mononuclear cells. Changes in cytokine secretions were related to clinical response to immunotherapy. Results: Controls had significantly higher mean IFN-y secretion compared to asthmatics (P < 0.01). Mean IL-10 secretion was lower in controls than in asthmatics, but significant levels were noted only with grass allergen (P < 0.03). In asthmatics, 3 months after starting immunotherapy mean IFN-y secretion significantly increased (P < 0.01) in both stimulated and unstimulated cells, which persisted at 6 months. Although there was no significant change in IL-10 secretion at 3 months, mean IL-10 secretion at 6 months was significantly decreased in allergen-stimulated cells (P < 0.02). Conclusion: In atopic asthmatics, mean IFN-y secretion significantly increased and allergen-specific IL-10 secretion was significantly decreased during immunotherapy.
Local and systemic immunological parameters associated with remission of asthma symptoms in children
Allergy, Asthma & Clinical Immunology, 2012
The immunological and clinical parameters that are associated with asthma remission are poorly understood. The cytokine and local mediator changes associated with the resolution of asthma symptoms were examined in three groups of subjects 12-18 years of age (n = 15 in each group): (a) continuing asthma group (CA) who had persistent symptoms since early childhood, (b) an age, sex and atopic status-matched group who had persistent symptoms in early childhood but in whom these had resolved (RA), and (c) a non-atopic, non-asthmatic control group. Clinical parameters, sputum cell counts, peripheral blood mononuclear cell (PBMC) cytokine production and activation marker expression were determined. All of the CA had methacholine airway hyperresponsiveness compared with only half of the RA subjects. The CA showed elevated numbers of eosinophils and increased ECP and IL-5 in sputum, which were not observed in the RA. PBMC cytokine studies revealed increased production of the type 1 cytokines IL-12, IFN-γ and TNF-α in the CA group compared with the RA group, under a range of activation conditions, however, the production of IL-4 and IL-5 were unchanged. These findings suggest that decreased type 1 cytokine expression as well as decreased eosinophilic inflammation is associated with the resolution of asthma symptoms.
Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy, 1998
Background The underlying mechanisms of immunotherapy (IT) are still unknown but may be related to modifications of cytokine production of T lymphocytes. Objective In this study we determined the in vitro allergen-induced production of IL-2, IL-4, IL-5, IL-12 and IFNg of peripheral blood mononuclear cells (PBMC) of eight young asthmatics, aged 15 Ϯ 2 years, receiving IT (IT group) and of eight comparable asthmatics, aged 13 Ϯ 3.5 years, who never received IT (non-IT group). Methods All patients suffered from perennial asthma and were allergic to house dust mite (HDM). They were selected if they showed a positive stimulation index (SI) of PBMC after in vitro incubation with HDM (i.e. SI > 2). Cells were incubated with and without HDM (10 mg/mL) during 24 h, 48 h and 7 days. Cytokines were determined in the supernatant at the three time points and are expressed as median values in pg/mL. Results In the IT group the secretion of IL-2 was lower compared with the non-IT group after 7 days incubation of PBMC with HDM (0 vs 33.2, P ¼ 0.008). In both groups maximal secretion of IL-2 was observed after 48 h. In the non-IT group a high value of IL-2 persisted after 7 days, whereas in the IT group a significant decline of IL-2 occurred after 7 days. Although IL-4 secretion was low in all subjects, more patients of the non-IT group showed detectable IL-4 in the HDM cultures after 24 h and 48 h, although the difference was not statistically significant (P ¼ 0.08 and P ¼ 0.28, respectively). Furthermore, IL-4 secretion was lower in the HDM cultures after 24 h in the IT group (1.75 vs 4.1, P ¼ 0.011) and 48 h (2.2 vs 4.1, P ¼ 0.035). IL-5 secretion was lower in the HDM cultures after 24 h (12.4 vs 47.6, P ¼ 0.035) and 48 h (26.8 vs 135, P ¼ 0.046) in the IT group than in the non-IT group. After 7 days of incubation with HDM there was no difference between the groups. There was no difference between both groups in secretion of IFNg and IL-12. Conclusions These results show a difference in vitro cytokine secretion of PBMC of asthmatics receiving IT compared with asthmatics who never received IT. PBMC of patients receiving IT secrete less IL-2 and IL-5 after in vitro incubation with HDM and show a tendency to secrete less IL-4. The efficacy of IT may be attributed to a modified cytokine secretion of PBMC.
Journal of Allergy and Clinical Immunology, 1997
Baekground: Allergic asthma is increasing in blaek South Africans, a cohort with inherently high basal IgE levels. Atopy has been linked to an excess of the T helper 2 cytokines IL-4 and IL-5 relative to the T helper 1 cytokine interferon-~ (IFN-~/); however, most studies have utilized T cell clones. Studies on peripheral blood mononuclear cells (PBMC) have shown decreased IFN-',/release in patients with atopic dermatitis. It is uncertain whether this finding extends to atopic asthma. Objectives: To characterize cytokine release by mitogen-activated PBMC from Xhosa children and to investigate whether reduced IFN-~/release is a feature of atopic asthma and whether there is a relationship between cytokine profiles and asthma severity. Methods: Cytokine release and proliferation of phytohemagglutinin-stimulated PBMC from 10 patients with severe asthma and 14 patients with moderate asthma (highly allergic to house dust mites) and 17 healthy controls was assessed. Total serum, allergen-specific, and Ascaris-specific IgE was measured. Results: Proliferation did not dilfer between the groups. The release of IFN-~/was progressively decreased (and the IL-4/ IFN-~/ratio increased) in the groups with moderate or severe asthma. Tumor necrosis factor-t~ release was reduced, but IL-4, IL-5, and granulocyte-macrophage-colony stimulating factor release was unchanged. The presence of Ascaris-specific IgE did not influence the cytokine profiles. Conclusion: Our study extends the findings observed for other atopic disorders and suggests that defective IFN-~, release is a generalized feature of atopic diseases. This study-the first to investigate both severe and moderate asthma, with the groups having similar atopic profiles-indicates that the extent of the defect in IFN-~/release might be related to asthma severity.