scholarly journals Expression of Surface Markers on the Blood Cells during the Delayed Asthmatic Response to Allergen Challenge

2014 ◽  
Vol 5 (2) ◽  
pp. ar.2014.5.0087 ◽  
Author(s):  
Zdenek Pelikan
Keyword(s):  
Nk Cells ◽  
Blood Cells ◽  
Allergen Challenge ◽  
Surface Markers ◽  
Asthmatic Response ◽  
Bronchial Challenge ◽  
Late Asthmatic Response ◽  
The Mean ◽  
Hypersensitivity Mechanism ◽  
Bronchial Allergen Challenge

Patients with bronchial asthma develop various types of asthmatic response to bronchial challenge with allergen, such as immediate/early asthmatic response (IAR), late asthmatic response (LAR) or delayed asthmatic response (DYAR), because of different immunologic mechanisms. The DYAR, occurring between 24 and 56 hours after the bronchial allergen challenge (p < 0.01), differs from IAR and LAR in clinical as well as immunologic features. This study investigates the expression of CD molecules (markers) on the surface of particular cell populations in the peripheral blood and their changes during the DYAR. In 17 patients developing the DYAR (p < 0.01), the bronchial challenge with allergen was repeated 2–6 weeks later. The repeated DYAR (p < 0.001) was combined with recording of CD molecule expression on various types of blood cells by means of flow cytometry up to 72 hours after the challenge. The results were expressed in percent of the mean relative fluorescence intensity. The DYAR was accompanied by (a) increased expression of CD11b, CD11b/18, CD16, CD32, CD35, CD62E, CD62L, CD64, and CD66b on neutrophils; CD203C on basophils; CD25and CD62L on eosinophils; CD14, CD16, CD64, and CD86 on monocytes; CD3, CD4, CD8, CD11a, CD18, and CD69 on lymphocytes; CD16, CD56, CD57, and CD94 on natural killer (NK) cells; and CD31, CD41, CD61, CD62P, and CD63 on thrombocytes and (b) decreased expression of CD18 and CD62L on eosinophils, CD15 on neutrophils, and CD40 on lymphocytes. These results suggest involvement of cell-mediated hypersensitivity mechanism, on participation of Th1- lymphocytes, neutrophils, monocytes, NK cells, and thrombocytes in the DYAR.

scholarly journals Delayed Asthmatic Response to Allergen Challenge and Cytokines Released by Nonspecifically Stimulated Blood Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Zdenek Pelikan
Keyword(s):  
Blood Cells ◽  
Allergen Challenge ◽  
Th1 Cells ◽  
Asthmatic Response ◽  
Asthma Patients ◽  
Additional Role ◽  
Bronchial Allergen Challenge ◽  
Support Evidence

Background. Bronchial asthma patients can develop various asthmatic response types following bronchial allergen challenge, such as immediate (IAR), late (LAR), dual late (DLAR), or delayed (DYAR), due to different immunologic mechanisms. The DYAR, recorded in 24 patients, beginning between 26 and 32 hrs and lasting up to 56 hrs after the bronchial allergen challenge, differs from the IAR, LAR, and DLAR in clinical, diagnostic, and immunologic aspects. Objective. To investigate amounts of particular cytokines released by the blood cells after an additional nonspecific stimulation with Phorbol 12-myristate 13-acetate (PMA) during the DYAR. Methods. In 24 patients, the repeated DYAR was supplemented with determination of cytokines both in the nonstimulated plasma and in the supernatants of the blood cells stimulated with PMA before and up to 72 hours after the bronchial challenge, by means of enzyme-linked immunoassay. Results. No significant changes of the prechallenge cytokine concentrations in the non-stimulated serum were recorded in the DYAR patients as compared with the healthy subjects. The DYAR was accompanied by significantly increased postchallenge concentrations (P<0.05) of IL-2, IL-8, IL-12p70, IL-13, IL-18, IFN-γ, G-CSF, TNF-α, and TGF-β, while decreased concentration of IL-7 (P<0.05) in the nonstimulated plasma. The significantly increased postchallenge concentrations of IL-2, IL-8, IL-12p70, IL-13, IL-18, IFN-γ, TNF-α, and TGF-β were released by peripheral blood cells after stimulation with PMA, as compared with both their prechallenge concentrations and with the PBS control values. Conclusions. These results would support evidence for an important role of the Th1 cells, neutrophils, monocytes, and probably also NK cells in the immunologic mechanism(s) leading to the development of the clinical DYAR. Nevertheless, an additional role of macrophages, endothelial and epithelial cells in these mechanisms cannot be even excluded.

scholarly journals Intranasal GSK2245035, a Toll-like receptor 7 agonist, does not attenuate the allergen-induced asthmatic response in a randomized, double-blind, placebo-controlled experimental medicine study

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0240964
Author(s):  
Hilary Siddall ◽  
Diana Quint ◽  
Hitesh Pandya ◽  
Will Powley ◽  
Shaila Shabbir ◽  
...  
Keyword(s):  
Allergic Asthma ◽  
Posterior Probability ◽  
Allergen Challenge ◽  
Toll Like Receptor ◽  
Weighted Mean ◽  
Double Blind ◽  
Asthmatic Response ◽  
Late Asthmatic Response ◽  
Bronchial Allergen Challenge

Background Allergic asthma is a heterogenous disorder predominantly driven by a type 2 inflammatory response to aeroallergens. Therapeutic modulation to rebalance these type 2 responses may offer clinical benefit for allergic respiratory inflammatory diseases, with the potential for disease modification. GSK2245035, a selective toll-like receptor-7 agonist, preferentially stimulates the induction of type 1 interferon alpha, reducing type 2 responses. Objective This study investigated whether intranasal GSK2245035 reduced allergen-induced bronchial reactivity in mild allergic asthma. Methods This double-blind, placebo-controlled, parallel-group Phase IIa trial randomized (1:1) participants with mild allergic asthma to intranasal GSK2245035 20 ng or placebo once weekly for 8 weeks; follow-up was conducted 1, 4, and 12 weeks after treatment. Allergen-induced late asthmatic response 1 week after treatment was measured as minimum and weighted mean forced expiratory volume in 1 second (FEV1) 4–10 hours following bronchial allergen challenge (primary endpoint). Pharmacodynamic and allergic biomarkers, and adverse events, were assessed. A Bayesian analysis framework was used; a posterior probability >0.7 denoted primary endpoint success. Results Thirty-six participants were randomized (GSK2245035, n = 22; placebo, n = 14). The percentage attenuation in late asthmatic response was –4.6% (posterior probability: 0.385) and –10.5% (posterior probability: 0.303) for minimum and weighted mean FEV1, respectively. Type 2 responses were confirmed by changes in lung function, eosinophils (blood and sputum), interleukin-5 (sputum) and fractional exhaled nitric oxide biomarkers pre- and post-bronchial allergen challenge. However, no treatment effect was observed. Adverse events were reported by 10/14 (71%) and 21/22 (95%) participants in the placebo and GSK2245035 groups, respectively; headache was the most common. Conclusions and clinical relevance Although target engagement was observed, weekly intranasal GSK2245035 20 ng for 8 weeks did not substantially attenuate the late asthmatic response in participants with mild allergic asthma. Overall, treatment was well tolerated.

scholarly journals Protective Effects of Fluticasone on Allergen-Induced Airway Responses and Sputum Inflammatory Markers

2000 ◽  
Vol 7 (4) ◽  
pp. 313-319 ◽  
Author(s):  
Krishnan Parameswaran ◽  
Mark D Inman ◽  
Rick M Watson ◽  
Marilyn M Morris ◽  
Ann Efthimiadis ◽  
...  
Keyword(s):  
Single Dose ◽  
Protective Effect ◽  
Allergen Challenge ◽  
Airway Responsiveness ◽  
Protective Effects ◽  
Asthmatic Response ◽  
Sputum Eosinophilia ◽  
Late Asthmatic Response ◽  
Cell Counts ◽  
Allergen Inhalation

BACKGROUND:A direct comparison of the protective effects of single and regular doses of inhaled glucocorticoid on allergen-induced asthmatic responses and inflammation has not been made.OBJECTIVE:To compare the effects of pretreatment with fluticasone 250 µg 30 min before allergen inhalation and two weeks of 250 µg twice daily (last dose 24 h before challenge) with single and regular (twice daily) placebo doses on early and late asthmatic responses, induced sputum cell counts and measures of eosinophil activation at 7 h and 24 h, and methacholine airway responsiveness at 24 h.PATIENTS AND METHODS:Ten mild asthmatic patients were studied in a randomized, double-blind, placebo controlled crossover study.RESULTS:Regular fluticasone increased the baseline mean provocative concentration of methacholine to cause a 20% fall (PC20) in forced expiratory volume in 1 s (FEV1) from 2.6 to 6.4 mg/mL (P<0.05) and lowered the eosinophil count from 3.1% to 0.4% (P<0.05) compared with regular placebo. Neither single nor regular fluticasone had any effect on the early asthmatic response. Single fluticasone attenuated the late asthmatic response, the mean ± SEM maximum percentage fall in FEV1(10.8±3.6 compared with single placebo 18.8±3.5, P=0.03), the allergen-induced increase of airway responsiveness (P<0.05), and the eosinophilia (P<0.005) and activated eosinophils at 7 h (P<0.01) but not at 24 h. Regular fluticasone also attenuated the late asthmatic response (11.1±2.5) compared with regular placebo (19.6±4.5), but this was not statistically significant and did not protect against the induced increase in airway responsiveness or the sputum eosinophilia.CONCLUSION:Two weeks of regular inhaled fluticasone discontinued 24 h before allergen challenge does not offer any additional protection against the early or late asthmatic responses, increased airway responsiveness or sputum eosinophilia compared with a single dose of 250 µg immediately before allergen challenge, despite increasing baseline PC20and decreasing sputum eosinophilia prechallenge. The significance of the protective effect of a single dose of inhaled steroid before an allergen inhalation and the duration of the protective effect need further investigation.

BECLOMETHASONE GIVEN AFTER THE EARLY ASTHMATIC RESPONSE INHIBITS THE LATE RESPONSE AND THE INCREASED METHACHOLINE RESPONSIVENESS AND CROMOLYN DOES NOT

PEDIATRICS ◽  
1994 ◽  
Vol 94 (2) ◽  
pp. 267-267
Author(s):  
David F. Graft
Keyword(s):  
Single Dose ◽  
Late Phase ◽  
Allergen Challenge ◽  
Allergen Exposure ◽  
Phase Response ◽  
Atopic Asthma ◽  
Late Response ◽  
Double Blind ◽  
Asthmatic Response ◽  
Late Asthmatic Response

Purpose of the Study. To investigate whether beclomethasone or cromolyn provides any protection from the late asthmatic response if given after the allergen exposure. Methods. Ten patients with mild, stable, atopic asthma with late asthmatic responses entered a double blind, double dummy trial comparing a single dose of inhaled beclomethasone (500 µg), cromolyn (20 mg), and placebo administered 2 hours after allergen challenge on the severity of the late asthmatic response and the change in the log of PC20 methacholine. Findings. The late asthmatic response after beclomethasone of 7.3% ± 6.1% decrease in FEV1 was significantly less than that experienced after cromolyn (20.4% ± 15.2%) or placebo (26.4% ± 8.2%); cromolyn was not different than placebo. There was a trend for the change in log PC20 methacholine to be less following beclomethasone administration than that seen with placebo or cromolyn. Reviewer's Comments. It is well known that a single dose of cromolyn given before allergen exposure inhibits both the early and late phase response, whereas beclomethasone given prior to exposure will only prevent the late phase response. However, many individuals don't plan ahead well enough and need to know what medication should be taken if they have forgotten to take any pretreatment. This study indicates that, if bedomethasone, albeit in a dose equal to 12 puffs of the U.S. concentration, is taken even as late as 2 hours after the exposure, it can significantly inhibit the development of the late phase response. Cromolyn given at that time provides only minimal benefit.

Effect of the Erythrocyte Apheresis On Immunological Parameters in Sickle Cell Anemia Patients in Crisis Period.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4191-4191
Author(s):  
Yurdanur Kilinc ◽  
Ferda Tekinturhan ◽  
Birol Guvenc ◽  
Refik Burgut ◽  
Ilgen Sasmaz ◽  
...  
Keyword(s):  
Blood Cell ◽  
Nk Cells ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Conflicts Of Interest ◽  
Blood Perfusion ◽  
Body Volume ◽  
Surface Markers ◽  
Immunological Parameters ◽  
The Mean

Abstract Abstract 4191 PURPOSE: Erythrocyte apheresis is an effective therapy in the acute and chronic treatment of sickle cell anemia (SCA). The main goal of erythrocyte apheresis is to improve blood perfusion through reducing Hemoglobin S (HbS) to < %30 and keeping hemoglobin (Hb) at desired level. The aim of this study was to evaluate the effect of the erythrocyte apheresis on immunological parameters in SCA patients with crisis. METHODS Between February 2009 and June 2009, 37 patients (20 female / 17 male) received 44 apheresis treatments at Hemapheresis Unit of Cukurova University School of Medicine, Adana, Turkey. The median age was 22 (Range, 4-56) years and the mean body weight was 51.9±18.6 kilograms. The apheresis procedures were carried out using a Cobe Spectra Cell Separator. A mean of 1.77 body volume calculated red blood cell volumes were exchanged with a mean duration of 125.9±34.9 minutes (Table 1). Sickling negative and leukoreduced packed red cells were used for apheresis treatments. Hemoglobin electrophoreses, complete blood counts, immunoglobins, specific surface markers for T, B and natural killer (NK) cells were performed before and after each procedure. While three patients had a SCA-induced functional asplenia, none of the patients was HIV-seropositive. RESULTS The erythrocyte apheresis resulted in a decrease on white blood cell (WBC) counts as expected. Average pre and post apheresis WBC counts were 12883±5775/mm3 and 8506±3331/mm3 (p<0.001) respectively. Accordingly, a decrease in post procedure lymphocyte, monocyte and granulocyte counts was observed. Because small amounts of patient's plasma were removed with red blood cells during apheresis procedures, serum levels of immuglobulins were also decreased. CD3, CD4 and CD8 for T cells, CD11b for monocytes, CD20 for B cells, CD56 as a NK marker and CD45 for leukocytes were analyzed and all of surface markers showed an increase after erythrocyte apheresis. The average pre apheresis HbS level was 78.90±19.20%, whereas the mean post apheresis HbS level was found to be 23.85±13.27% (p<0.001) (Table 2). CONCLUSIONS The erythrocyte apheresis is an effective and rapid procedure to reduce HbS concentration without increasing blood viscosity. Apheresis treatments have also been found to be beneficial in decreasing the leukocyte counts and serum immunoglobulins levels in the blood. Flow cytometric analyses revealed that T, B and NK cells were increased after apheresis treatment. Interestingly, the change in CD4/CD8 ratio was not statistically significant (p>0.05). This shows that vascular wall integrity is maintained and apheresis can be safely performed in SCA patients. In our study, blood perfusion was restored and blood chemistry was improved to optimal levels after erythrocyte apheresis. As a result, crisis periods were shortened. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Development of Asthmatic Response upon Bronchial Allergen Challenge Is Associated with Dynamic Changes of Interleukin-10-Producing and Interleukin-10-Responding CD4+ T Cells

Inflammation ◽  
2014 ◽  
Vol 37 (6) ◽  
pp. 1945-1956 ◽  
Author(s):  
Marcin Moniuszko ◽  
Kamil Grubczak ◽  
Krzysztof Kowal ◽  
Andrzej Eljaszewicz ◽  
Malgorzata Rusak ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Allergen Challenge ◽  
Interleukin 10 ◽  
Dynamic Changes ◽  
Asthmatic Response ◽  
Bronchial Allergen Challenge
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