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Canonica GW, Busse W, Fabbri L, et al., 1997, Inflammation: Rhinitis and asthma, Pages: 286-287, ISSN: 0905-9180
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- Citations: 4
Szczeklik A, Barnes P, Wayoff M, et al., 1997, Aspirin sensitivity, rhinitis and asthma, Pages: 292-293, ISSN: 0905-9180
Busse W, Buist S, Mygind N, et al., 1997, Epidemiology of rhinitis and asthma, Pages: 284-285, ISSN: 0905-9180
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- Citations: 14
Van Cauwenberge P, Holgate S, Bousquet J, et al., 1997, Diagnosis in rhinitis coexisting with asthma, Pages: 288-291, ISSN: 0905-9180
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- Citations: 10
Mygind N, Davies R, Canonica GW, et al., 1997, Rhinitis and asthma: Treatment options, Pages: 296-299, ISSN: 0905-9180
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- Citations: 1
Kharitonov SA, Rajakulasingam K, OConnor B, et al., 1997, Nasal nitric oxide is increased in patients with asthma and allergic rhinitis and may be modulated by nasal glucocorticoids, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 99, Pages: 58-64, ISSN: 0091-6749
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- Citations: 219
Humbert M, Ying S, Corrigan C, et al., 1997, Bronchial mucosal expression of the genes encoding chemokines RANTES and MCP3 in symptomatic atopic and nonatopic asthmatics: Relationship to the eosinophil-active cytokines interleukin (IL)-5, granulocyte macrophage-colony-stimulating factor, and IL-3, AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, Vol: 16, Pages: 1-8, ISSN: 1044-1549
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- Citations: 135
Grant JA, Humbert M, TabordaBarata L, et al., 1997, High-affinity IgE receptor fc epsilon RI expression in allergic reactions, INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY, Vol: 113, Pages: 376-378, ISSN: 1018-2438
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- Citations: 3
Kay AB, Barata L, Meng Q, et al., 1997, Eosinophils and eosinophil-associated cytokines in allergic inflammation., Int Arch Allergy Immunol, Vol: 113, Pages: 196-199, ISSN: 1018-2438
Eosinophils are major effector cells in allergic tissue reactions. Their capacity to synthesize and store cytokines, particularly Th2-type cytokines, which may have autocrine effects such as increased cell survival in tissues, is of particular current interest. We have shown that eosinophils infiltrating the site of human cutaneous late-phase reactions (LPR) express mRNA and protein product for IL-4 and IL-5. Stimulation of peripheral blood eosinophils in vitro with either IgG or sIgA produces time-dependent induction of IL-4 and IL-5 transcription, indicating that mature cells may undergo local cytokine synthesis. We also demonstrated that bronchial biopsies from patients with both atopic and non-atopic (intrinsic) asthma express IL-4 and IL-5 mRNA which mainly co-localized to T cells, although clear hybridization signals were also obtained with eosinophils and mast cells. On the other hand, immunoreactivity for the corresponding protein was detectable predominantly in eosinophils and mast cells; a finding believed to reflect granule storage of cytokines. We also studied the resolution of the cutaneous LPR. Apoptosis of eosinophils persisted slightly longer than neutrophils in the tissues. The eventual decline in both neutrophil and eosinophil numbers followed on from the peak of the LPR. This was associated with terminal-deoxynucteotidyl-transferase-mediated nick and labelling positive (TUNEL+) (apoptotic) cells with the subsequent removal of apoptotic neutrophils and eosinophils by tissue macrophages. Thus, IL-4 and IL-5 production by eosinophils may amplify local allergic inflammatory responses and, in the case of IL-5, may prolong local tissue survival. However, in the allergen-induced LPR, inflammation rapidly resolves, possibly through the initiation of programmed cell death and phagocytosis of apoptotic cells by macrophages.
Durham SR, Gould HJ, Hamid QA, 1997, Local IgE production in nasal allergy, INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY, Vol: 113, Pages: 128-130, ISSN: 1018-2438
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- Citations: 62
Durham SR, Hamid QA, 1997, The effect of immunotherapy on allergen induced late responses., Pages: 33-39, ISSN: 0936-8671
Durham SR, 1996, Basic mechanisms of immunotherapy, Pages: 88-91, ISSN: 0214-1477
Powell N, Humbert M, Durham SR, et al., 1996, Increased expression of mRNA encoding RANTES and MCP-3 in the bronchial mucosa in atopic asthma, EUROPEAN RESPIRATORY JOURNAL, Vol: 9, Pages: 2454-2460, ISSN: 0903-1936
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- Citations: 52
Humbert M, Durham SR, Ying S, et al., 1996, IL-4 and IL-5 mRNA and protein in bronchial biopsies from patients with atopic and nonatopic asthma: evidence against "intrinsic" asthma being a distinct immunopathologic entity., Am J Respir Crit Care Med, Vol: 154, Pages: 1497-1504, ISSN: 1073-449X
Intrinsic (nonatopic) asthma is considered to be a distinct pathogenetic variant of asthma since, unlike extrinsic (atopic) asthma, patients with the disease are skin test-negative to common aeroallergens, and have total serum IgE concentrations within the normal range. Nevertheless, the recent demonstration of increased numbers of cells expressing the high-affinity IgE receptor in bronchial biopsies from atopic and nonatopic asthmatic subjects, together with epidemiologic evidence indicating that serum IgE concentrations relate closely to asthma prevalence regardless of atopic status, suggests that IgE-mediated mechanisms may participate in the pathogenesis of both atopic and nonatopic asthma. Furthermore both variants of the disease are associated with bronchial mucosal eosinophilic inflammation. Interleukin-4 (IL-4) is an essential cofactor for IgE synthesis, and there is strong evidence that IL-5 plays a major role in eosinophil accumulation in asthmatic inflammation. For these reasons we compared the expression of IL-4 and IL-5 mRNA and protein product using a semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) amplification, in situ hybridization, and immunohistochemistry in bronchial biopsies from symptomatic atopic and nonatopic asthmatic subjects and atopic and nonatopic controls. The results showed that as compared with controls, biopsies from both groups of asthmatic subjects had increased numbers of IL-4 and IL-5 mRNA copies relative to beta-actin mRNA as detected by RT-PCR. Similarly, in situ hybridization and immunohistochemistry demonstrated increased numbers of cells expressing IL-4 and IL-5 mRNA and protein in asthmatic subjects, irrespective of their atopic status. We conclude that individuals with either atopic or nonatopic asthma show infiltration of the bronchial mucosa with cells expressing Th2-type cytokines, providing further evidence for similarities in the immunopathogenesis of these clinically distinct forms of asthma
Passalacqua G, Bousquet J, Bachert C, et al., 1996, The clinical safety of H1-receptor antagonists. An EAACI position paper., Allergy, Vol: 51, Pages: 666-675, ISSN: 0105-4538
Durham SR, 1996, Allergen avoidance measures, RESPIRATORY MEDICINE, Vol: 90, Pages: 441-445, ISSN: 0954-6111
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- Citations: 10
Durham SR, 1996, Allergen avoidance measures. British Thoracic Society., Respir Med, Vol: 90, Pages: 441-445, ISSN: 0954-6111
Bentley AM, Walker S, Hanotte F, et al., 1996, A comparison of the effects of oral cetirizine and inhaled beclomethasone on early and late asthmatic responses to allergen and the associated increase in airways hyperresponsiveness., Clin Exp Allergy, Vol: 26, Pages: 909-917, ISSN: 0954-7894
BACKGROUND: Cetirizine is a non-sedating H1 antihistamine which is effective in the treatment of allergic rhinitis and urticaria. It inhibits eosinophil and basophil chemotaxis in late cutaneous allergic reactions in skin windows. Its effect on early (EAR) and late asthmatic reactions (LAR) is less certain. METHODS: We examined the effect on EAR and LAR of 3 days treatment with oral cetirizine (15 mg twice daily) compared with a single dose of inhaled beclomethasone 10 min prior to allergen challenge in a placebo-controlled (oral and inhaled) double-blind cross-over design with three treatment arms separated by 14 days. RESULTS: Cetirizine did not significantly inhibit either the EAR or LAR documented by maximum percentage fall in FEV1 (0-3 and 6-9 h) or as area under the curve (AUC between 0 and 3 and 6-9 h). Beclomethasone inhibited the LAR compared with placebo (P = 0.02) when expressed as AUC (6-9 h). This did not quite reach statistical significance (P = 0.06) when expressed as maximal percentage late fall in FEV1 between 6 and 9 h. A greater than twofold increase in airways responsiveness to methacholine was observed 3 h after challenge which was significantly reduced by beclomethasone compared with placebo (P < 0.02) and cetirizine (P < 0.05). The data suggest that oral cetirizine does not significantly inhibit either the EAR or LAR. Beclomethasone inhibited both the early increase in airways responsiveness and the subsequent LAR. Our study also confirms the view that early increases in airway responsiveness precede the late response and suggests that these associated events are not dissociable by the pharmacological treatments employed in this study.
Humbert M, Robinson DS, Assoufi B, et al., 1996, Safety of fibreoptic bronchoscopy in asthmatic and control subjects and effect on asthma control over two weeks., Thorax, Vol: 51, Pages: 664-669, ISSN: 0040-6376
BACKGROUND: Concerns remain about the safety of bronchoscopy in asthma and there are few data on the effect of this procedure on asthma control in the days or weeks following bronchoscopy. METHODS: In an initial study of bronchoalveolar lavage and bronchial biopsies in asthmatic and control subjects, data on peak expiratory flow rates (PEFR) collected prospectively before and after the procedure were available from 21 of the 29 asthmatic subjects studied. These showed a median 23% fall in PEFR from baseline after bronchoscopy (range 3-58%). To determine whether this fall in PEFR following bronchoscopy reflected bronchospasm or the effect of sedation, PEFR and spirometric tests were performed during the two hours following bronchoscopy in a further study of 15 symptomatic asthmatic subjects and 20 non-asthmatic controls. To examine the effect on asthma control, asthmatic patients recorded PEFR, symptom scores, and medication use for two weeks before and after bronchoscopy. RESULTS: After bronchoscopy with bronchial biopsies there was no difference between the median maximal fall in either PEFR or arterial oxygen saturation between the 15 asthmatic patients (10.4% and 4%, respectively) and 20 controls (12% and 3%). Moreover, there were no significant changes in PEFR, symptom score, or medication use by the asthmatic subjects in the two weeks after bronchoscopy when compared with the two weeks before bronchoscopy. CONCLUSIONS: Fibreoptic bronchoscopy is well tolerated in asthmatic subjects. Falls in PEFR in both asthmatic and non-asthmatic subjects after bronchial biopsy may reflect the effects of sedation rather than bronchospasm. Additional bronchoalveolar lavage may cause bronchoconstriction. Careful monitoring is therefore essential. Peak flow monitoring up to two weeks after bronchoscopy with bronchial biopsy revealed no delayed effects on asthma control.
Humbert M, Grant JA, Taborda-Barata L, et al., 1996, High-affinity IgE receptor (FcepsilonRI)-bearing cells in bronchial biopsies from atopic and nonatopic asthma., Am J Respir Crit Care Med, Vol: 153, Pages: 1931-1937, ISSN: 1073-449X
Asthma is characterized by bronchial mucosal inflammation. Although allergen-induced activation of cells binding allergen-specific immunoglobulin E (IgE) through high-affinity receptors (Fc(epsilon)RI) is believed to play some role in asthma, inappropriate synthesis of total or allergen-specific IgE cannot be demonstrated in some ("intrinsic") patients despite the fact that the nature of the bronchial inflammation is similar to that in atopic ("extrinsic") asthmatics. We have studied the numbers and phenotype of Fc(epsilon)RI-bearing cells in bronchial biopsies from 12 atopic and 10 nonatopic asthmatic patients and compared our findings with 10 atopic and 12 nonatopic control subjects using single and double immunohistochemistry. Significantly increased numbers of Fc(epsilon)RI-bearing cells were identified in bronchial biopsies from atopic and nonatopic asthmatics and atopic control subjects when compared with normal controls (p = 0.001, 0.006, and 0.0006, respectively). In asthmatics and atopics the majority of Fc(epsilon)RI-bearing cells were identified as mast cells and macrophages; a much smaller percentage were eosinophils. We conclude that elevated numbers of high-affinity IgE receptor-bearing cells are a feature of bronchial biopsies of asthmatic subjects, irrespective of their atopic status.
Durham SR, Ying S, Varney VA, et al., 1996, Grass pollen immunotherapy inhibits allergen-induced infiltration of CD4(+) T lymphocytes and eosinophils in the nasal mucosa and increases the number of cells expressing messenger RNA for interferon-gamma, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 97, Pages: 1356-1365, ISSN: 0091-6749
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- Citations: 334
Robinson DS, Tsicopoulos A, Meng Q, et al., 1996, Increased interleukin-10 messenger RNA expression in atopic allergy and asthma., Am J Respir Cell Mol Biol, Vol: 14, Pages: 113-117, ISSN: 1044-1549
Interleukin-10 (IL-10) inhibits T-lymphocyte proliferation and production of cytokines. We have examined expression of IL-10 messenger RNA (mRNA) in atopic asthma and in allergen and tuberculin skin responses by in situ hybridization. The proportion of bronchoalveolar lavage (BAL) cells positive for IL-10 mRNA was increased in a group of 10 symptomatic asthmatics when compared with control subjects (17.5% versus 5.2% BAL cells positive; P < 0.001). In a separate group of six mild atopic asthmatics, there was an increased proportion of BAL cells positive for IL-10 mRNA 24 h after allergen inhalation challenge compared with diluent challenge BAL from the same subjects (24% versus 10%; P < 0.005). By simultaneous in situ hybridization and immunocytochemistry, IL-10 mRNA was localized to both CD3+ T cells and CD68+ alveolar macrophages in BAL, with a significantly more prominent T-cell signal in the symptomatic asthmatics compared with control subjects and after allergen challenge compared with diluent challenge of the mild asthmatic subjects. It has been suggested that IL-10 production is a late event after T-cell activation. To examine kinetics and specificity of IL-10 mRNA expression, skin biopsies were obtained from atopic, tuberculin-sensitive subjects at 1, 6, and 48 h after cutaneous injection of allergen or tuberculin. With both stimuli, there was an increase in IL-10 mRNA-positive cells at 6 h when compared with control sites injected with appropriate diluent which were biopsied 24 h after injection (P < 0.01 for allergen and P < 0.02 for tuberculin). These findings are compatible with the hypothesis that IL-10 mRNA is expressed in both macrophages and T lymphocytes in the airway in asthma and that IL-10 mRNA expression is induced from T lymphocytes in response to allergen. This response may also occur in other types of cell-mediated inflammation.
Bentley AM, Hamid Q, Robinson DS, et al., 1996, Prednisolone treatment in asthma. Reduction in the numbers of eosinophils, T cells, tryptase-only positive mast cells, and modulation of IL-4, IL-5, and interferon-gamma cytokine gene expression within the bronchial mucosa., Am J Respir Crit Care Med, Vol: 153, Pages: 551-556, ISSN: 1073-449X
We have tested the hypothesis that the beneficial effects of corticosteroids in asthma may result from reduction in the number of inflammatory cells infiltrating the bronchial mucosa with inhibition of cytokine gene expression. A randomized parallel group study was performed in 18 moderately severe asthmatic patients in whom an elective trial of corticosteroid treatment was indicated. Fiberoptic bronchoscopy was performed and bronchial biopsies taken from segmental carinae before and after 2 wk treatment with prednisolone (0.6 mg/kg/d) or matched placebo tablets. Immunohistology was performed on 6-microns cryostat sections using monoclonal antibodies. The number of cells expressing cytokine messenger RNA (mRNA) was assessed by in situ hybridization using S35-labeled riboprobes. When prednisolone- and placebo-treated groups were compared there was a decrease in airway methacholine responsiveness (p < 0.01) and an increase in FEV1 (p < 0.05) after prednisolone. This was accompanied by a reduction in CD3+ T lymphocytes (p < 0.05), "activated" EG2+ eosinophils (p < 0.02), and tryptase-only (mucosal-type) MCT cells (p < 0.02) but not MCTC (tryptase+chymase positive) cells in prednisolone-treated patients. In prednisolone-treated patients there was also a reduction in the number of cells expressing mRNA for interleukin-4 (IL-4, p < 0.01), and interleukin-5 (IL-5, p < 0.03) and an increase in cells expressing mRNA for interferon-gamma (IFN-gamma) (p < 0.01). These results support the view that corticosteroid treatment in asthma may act by modulation of cytokine expression with consequent inhibition of the local bronchial inflammatory infiltrate and tissue eosinophilia.
Ying S, Meng Q, Taborda-Barata L, et al., 1996, Human eosinophils express messenger RNA encoding RANTES and store and release biologically active RANTES protein., Eur J Immunol, Vol: 26, Pages: 70-76, ISSN: 0014-2980
Eosinophils synthesize and store various cytokines with potential autocrine activity. We hypothesized that eosinophils synthesize and store RANTES, a CC-chemokine with potent eosinophil chemotactic activity. Expression of RANTES mRNA in highly purified eosinophil populations was detected by reverse transcription followed by polymerase chain reaction analysis. In situ hybridization (ISH) with 35S-labeled RANTES-specific riboprobes showed that 6.8-10% of peripheral blood eosinophils obtained from atopic subjects expressed RANTES mRNA, increasing to 25% after incubation (16 h) with interferon (IFN)-gamma, but not ionomycin in vitro. Peripheral blood eosinophils also showed specific immunoreactivity with an anti-RANTES monoclonal antibody, consistent with translation of the mRNA. By enzyme-linked immunosorbent assay, blood eosinophils were shown to contain a median of 7300 pg (range 5200-8800) RANTES per 10(6) cells, of which a mean of 24% was released into culture supernatants after stimulation of the cells with serum-coated particles in vitro. These culture supernatants exhibited eosinophil chemotactic activity which was inhibited (mean 68%) by a specific anti-RANTES antibody. Sequential immunocytochemistry and ISH on biopsies obtained from allergen-induced late-phase cutaneous reactions showed that 55-75% of the infiltrating RANTES mRNA+ cells were EG2+ eosinophils. Allergen, but not diluent challenge, was also associated with a time-dependent increase in the number of cells showing RANTES immunoreactivity. Of these cells, 55% were identified as eosinophils by morphological criteria. Thus, human eosinophils have the capacity to synthesize, store and secrete physiologically relevant quantities of RANTES, and may therefore be an important source of this chemokine in allergic inflammation.
Taborda-Barata L, Jacobson M, Walker S, et al., 1996, Effect of cetirizine and prednisolone on cellular infiltration and cytokine mRNA expression during allergen-induced late cutaneous responses., Clin Exp Allergy, Vol: 26, Pages: 68-78, ISSN: 0954-7894
BACKGROUND: The ability of cetirizine to inhibit eosinophil infiltration into the sites of allergen-induced cutaneous late-phase reactions is controversial. A previous skin biopsy study gave negative results with 15 mg of cetirizine as a single dose. OBJECTIVE: To confirm these findings we have used cetirizine (30 mg daily) for 5 days and compared the results with prednisolone (20 mg daily for 5 days) as a positive control. The effect of these agents on mRNA positive cells for interleukin-3 (IL-3), interleukin-4, interleukin-5 and granulocyte/macrophage-colony stimulating factor (GM-CSF) was also evaluated. METHODS: A double-blind, placebo-controlled cross-over study (n = 12) was followed. After each treatment 30 biological units (BUs) of Dermatophagoides pteronyssinus or Phleum pratense were injected intradermally and the early (15 min) and late-phase response sizes (6 and 24 h) were measured. Skin biopsies were taken at 24 h for immunocytochemistry and in situ hybridization. RESULTS: Cetirizine but not prednisolone inhibited the early-phase response (37%, P = 0.004). In contrast prednisolone, but not cetirizine, significantly inhibited the size of the late-phase reaction at 24 h (70%, P = 0.021). This was associated with significant decreases in total (MBP+) and activated (EG2+) eosinophils (P = 0.019 and 0.014, respectively), as compared with placebo. There were also clear but non-significant reductions in interleukin-3, interleukin-4, interleukin-5 and granulocyte/macrophage-colony stimulating factor mRNA+ cells. CONCLUSION: Prednisolone, but not cetirizine, inhibited both the magnitude of the allergen-induced late-phase response and the accompanying local eosinophil infiltration. These corticosteroid effects were associated with a reduction in cells expressing mRNA for 'TH2-type' cytokines.
MOQBEL R, YING S, BARKANS J, et al., 1995, IDENTIFICATION OF MESSENGER-RNA FOR IL-4 IN HUMAN EOSINOPHILS WITH GRANULE LOCALIZATION AND RELEASE OF THE TRANSLATED PRODUCT, JOURNAL OF IMMUNOLOGY, Vol: 155, Pages: 4939-4947, ISSN: 0022-1767
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- Citations: 192
Robinson DS, Assoufi B, Durham SR, et al., 1995, Eosinophil cationic protein (ECP) and eosinophil protein X (EPX) concentrations in serum and bronchial lavage fluid in asthma. Effect of prednisolone treatment., Clin Exp Allergy, Vol: 25, Pages: 1118-1127, ISSN: 0954-7894
BACKGROUND: Eosinophil granule proteins may contribute to bronchial hyperresponsiveness in asthma. OBJECTIVE: To measure eosinophil cationic protein (ECP) and eosinophil protein X (EPX) in serum and bronchial lavage fluid from 20 asthmatics and 16 control subjects. To assess the effect on these eosinophil proteins of corticosteroid treatment of asthma. To determine whether serum ECP and EPX measured weekly in a longitudinal study for 10 weeks reflected changes in lung function. METHODS: Eosinophil granule proteins were measured by radioimmunoassay of bronchial wash (BW), bronchoalveolar lavage (BAL) and serum. RESULTS: Eosinophils were elevated in BAL (P < 0.01), BW (P < 0.01) and blood (P < 0.01) from asthmatics compared with control subjects. Eosinophils cationic protein concentration was significantly elevated in BAL (P < 0.05) and BW from asthmatics (P < 0.01) and EPX was increased in BAL (P < 0.05) and BW (P < 0.01). These changes were also reflected in elevated serum ECP (P < 0.01) and EPX (P < 0.01) concentrations in asthmatic subjects. There was no significant difference between subjects receiving prednisolone and the placebo group, but there was a fall in ECP in BW (P < 0.05) and serum (P < 0.01) and in EPX in BW (P < 0.01) and serum (P < 0.01) within the group receiving prednisolone. In the longitudinal study there was only a significant difference between ECP values associated with highest and lowest peak expiratory flow rate (PEFR) (P < 0.05). CONCLUSIONS: These data confirm a role for eosinophil activation in the airway in asthma pathogenesis, and add some support to the hypothesis that corticosteroids may inhibit eosinophil activation in asthma.
Till S, Li B, Durham S, et al., 1995, Secretion of the eosinophil-active cytokines interleukin-5, granulocyte/macrophage colony-stimulating factor and interleukin-3 by bronchoalveolar lavage CD4+ and CD8+ T cell lines in atopic asthmatics, and atopic and non-atopic controls., Eur J Immunol, Vol: 25, Pages: 2727-2731, ISSN: 0014-2980
Specific eosinophil accumulation and activation within the asthmatic bronchial mucosa are thought to occur at least partly through the actions of cytokines, including interleukin (IL)-5, IL-3 and granulocyte/macrophage colony-stimulating factor (GM-CSF). Although mRNA encoding some of these cytokines has been demonstrated in bronchoalveolar lavage (BAL) fluid cells and bronchial biopsies from asthmatics, it has yet to be established whether these cells produce the translated products and whether expression is associated with CD4+ T helper or CD8+ cytotoxic T cells. We addressed this problem by raising polyclonal CD4+ and CD8+ T cell lines from the BAL fluid of six atopic asthmatics, five atopic non-asthmatics and seven non-atopic non-asthmatic controls. BAL fluid cells obtained at fiberoptic bronchoscopy were depleted of adherent cells, and then T lymphocytes expanded by stimulation with monoclonal anti-CD3 antibody and recombinant human IL-2. When lymphocytes had expanded to sufficient numbers, CD4+ and CD8+ cells were separated by positive selection with magnetic beads coated with anti-CD4 or anti-CD8 monoclonal antibodies and further expanded. Cytokine secretion by standardized cell numbers was measured by enzyme-linked immunosorbent assays. BAL CD4+ T cell lines from the asthmatics secreted significantly elevated quantities of both IL-5 and GM-CSF as compared with lines from the atopic and non-atopic controls (p = 0.023-0.003). In contrast, IL-3 secretion did not significantly differ between the groups. In some subjects, CD8+ T cell lines also secreted significant quantities of these cytokines and there was a trend for IL-5 secretion by these cells to be higher in asthmatics than non-atopic controls (p = 0.035). These data are consistent with the hypothesis that activated T lymphocytes from asthmatics, particularly of the CD4+ subset, are predisposed to release elevated quantities of cytokines relevant to the accumulation and activation of eosinophils.
Ying S, Durham SR, Corrigan CJ, et al., 1995, Phenotype of cells expressing mRNA for TH2-type (interleukin 4 and interleukin 5) and TH1-type (interleukin 2 and interferon gamma) cytokines in bronchoalveolar lavage and bronchial biopsies from atopic asthmatic and normal control subjects., Am J Respir Cell Mol Biol, Vol: 12, Pages: 477-487, ISSN: 1044-1549
We investigated the phenotype of cells expressing messenger RNA encoding interleukin 4 (IL-4), IL-5, IL-2, and interferon gamma (IFN-gamma) in bronchoalveolar lavage (BAL) and bronchial biopsies (BX) from seven mild atopic asthmatic patients and nine nonasthmatic controls. Immunocytochemistry followed by in situ hybridization using either 35S- or digoxigenin-labeled riboprobes was performed on cytospins from BAL and BX, respectively. With BAL or BX, in situ hybridization alone showed significant increases in percentages of IL-2, IL-4, and IL-5 mRNA+ cells when asthmatics were compared to nonasthmatic controls. Double immunocytochemistry-in situ hybridization revealed that > 70% of IL-4 and IL-5 mRNA+ cells were activated T cells (CD3+). The remaining IL-4 and IL-5 mRNA+ signals were colocalized to tryptase+ mast cells, and activated eosinophils (EG2+). Rare IL-4 and IL-5 mRNA+ cells were observed in nonasthmatic controls, the majority being CD3+ cells, as were IL-2 and IFN-gamma mRNA+ cells (in both asthmatics and controls). A few IL-4 (< 8%) and IL-5 (< 5%) mRNA+ signals did not colocalize with any of the cells identified by immunocytochemistry. Thus, we provide further evidence that CD3+ T cells are the most abundant cells expressing IL-4 and IL-5 mRNA in BAL and BX from allergic asthma. Fewer, but detectable, numbers of tryptase+ mast cells and EG2+ eosinophils also expressed these transcripts.
WALKER SM, VARNEY VA, GAGA M, et al., 1995, GRASS-POLLEN IMMUNOTHERAPY - EFFICACY AND SAFETY DURING A 4-YEAR FOLLOW-UP-STUDY, ALLERGY, Vol: 50, Pages: 405-413, ISSN: 0105-4538
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- Citations: 138
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