bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dysregulation of monocyte differentiation in asthmatic subjects is reversed by IL‐10
Authors: Tormey  , Leonard  , Faul  , Bernard  , Burke  , Poulter  
Published: March 2003

BackgroundIL‐10 can modulate the differentiation of normal monocytes to macrophages, increasing the proportion of maturing cells with a phenotype consistent with T cell suppressive activity. Analysis of the immunopathology in endobronchial biopsies from asthmatic subjects has revealed significantly reduced proportions of suppressive macrophage populations associated with chronic T‐cell mediated inflammation.ObjectiveThis study investigates whether the altered homeostasis within the lung macrophage populations in asthma is reflected in aberrant differentiation of peripheral blood monocytes and whether this differentiation may be influenced by IL‐10.MethodsMonocytes from 14 normal individuals and 14 atopic asthmatics were grown in culture for 7 days in the presence or absence of IL‐10, added on day 5. Double immunofluoresence studies were performed on cytospins of the differentiated macrophages using the monoclonal antibodies RFD1 and RFD7 to distinguish inductive and suppressive macrophages by their respective phenotypes. HLADR expression was quantified using the monoclonal antibody RFDR1. Macrophage function was determined by quantifying allostimulation in a mixed leucocyte reaction and by measuring TNFα and TGFβ production.ResultsWith no cytokine addition the proportion of maturing macrophages with a suppressive phenotype (D1+ D7+) at day 7 was lower in the asthmatic samples (18%) compared with normals (25%). IL‐10 increased the proportion of suppressive cells in cultures of both asthmatic and normal monocytes with the increase in the asthmatic subjects (94% increase) being significantly greater than that in normal subjects (32% increase) (P < 0.01). Asthmatic monocytes had a greater effect in stimulating MLR than normals (P < 0.05) but the addition of IL‐10 reduced T cell proliferation in an MLR to a equivalent level in both groups.ConclusionsThese results suggest that a fundamental problem may exist in the differentiation of monocytes in asthma which may be reversed by IL‐10.
Mast cell tryptase stimulates both human dermal fibroblast proliferation and type I collagen production
Authors: Abe  , Kurosawa  , Ishikawa  , Miyachi  , Kido  
Published: March 2003

BackgroundMast cell tryptase has been shown to be mitogenic for fibroblasts, however, it still remains unknown whether mast cell tryptase stimulates collagen production by human dermal fibroblasts.ObjectiveWe have investigated the effect of mast cell tryptase on type I collagen production by human dermal fibroblasts as well as the proliferation of the fibroblasts.MethodsTryptase isolated from human lung tissue was added to the culture of fibroblasts from normal dermis, and the fibroblast proliferation and the activity of type I collagen synthesis in the supernatants were assayed, respectively.ResultsFibroblast proliferation was increased with tryptase in a concentration‐dependent manner, and a significant increase was observed in the presence of tryptase at concentrations from 0.01 to 10 μg/mL. The increase of fibroblast proliferation with 3 μg/mL tryptase was significantly reduced by 15 μg/mL antitryptase IgG antibody, which was demonstrated to inhibit fibrinogenolysis of tryptase. On the other hand, the production of type I collagen by the fibroblasts was significantly increased with tryptase at a concentration of 10 μg/mL. The collagen production in the presence of 10 μg/mL tryptase was significantly inhibited by 50 μg/mL antitryptase IgG antibody.ConclusionTryptase increases not only the proliferation of human dermal fibroblasts but also type I collagen production.
Kinetics of apoptosis in the lung of mice with allergic airway inflammation
Authors: Kodama  , Matsuyama  , Miyata  , Nishimura  , Nishioka  , Kitada  , Sugita  
Published: March 2003

BackgroundApoptosis has been suggested as a means to facilitate the resolution of eosinophilic inflammation in bronchial asthma. However, the natural course of apoptosis has not been elucidated in vivo, and there is no direct evidence for eosinophilic apoptosis within lung tissue.ObjectiveThe purpose of this study is to clarify whether the apoptosis occurs within the lung tissue, and to define the time‐course of change in apoptosis ratio during the resolution of pulmonary eosinophilic inflammation.MethodsOvalbumin (OVA)‐sensitized Balb/c mice were challenged with aerosolized OVA. We studied apoptotic cells in the lung of OVA‐sensitized mice at 1, 3, 7 and 14 days after OVA challenge by in situ detection of DNA fragmentation with deoxynucleotidyl transferase deoxyuridyl triphosphatase nick endlabelling (TUNEL) technique. Apoptotic cells also were identified by electron microscopic analysis in the lung 7 days after OVA challenge.ResultsThe TUNEL‐method revealed that eosinophils localized in the subepithelium of bronchi undergo apoptosis following OVA challenge. Electron microscopy confirmed the presence of apoptotic cells, apoptotic bodies, and macrophages ingesting apoptotic bodies within the lung tissue. The number of apoptotic cells increased concomitantly with the increase in eosinophilic infiltration for 3 days post‐challenge. However, both the apoptotic cell counts and the apoptotic ratio continued to increase even after the eosinophil count peaked, indicating rather late induction of apoptosis in the lung. In addition, TUNEL‐positive cells were localized in the lung for 14 days post‐challenge, indicating prolonged induction of apoptosis after the OVA challenge.ConclusionOur findings constitute direct evidence of eosinophilic apoptosis in situ, and display the kinetics of apoptosis in the lung of the allergic inflammation.
Expression of two isoforms of Lep d 2, the major allergen of Lepidoglyphus destructor, in both prokaryotic and eukaryotic systems
Authors: Olsson  , Van Hage‐Hamsten  , Whitley  , Johansson  , Hoffman  , Gafvelin  , Schmidt  
Published: March 2003

BackgroundThe dust mite Lepidoglyphus destructor is a major cause of allergic diseases among farmers. We have previously cloned and sequenced two isoforms of the major allergen Lep d 2 (formerly designated Lep d 1) and found significant homology to group 2 allergens of the house dust mite species Dermatophagoides. We now report on the production and characterization of recombinant Lep d 2.ObjectiveWe have expressed both isoforms in two different expression systems; a eukaryotic system, baculovirus in insect cells and a prokaryotic system, E. coli. We have compared the two systems in regard to production yields and immunoreactivity of the recombinant allergens.MethodsThe complete cDNA including the natural leader sequence was cloned into the pBlueBacIII transfer vector, and the rLep d 2 was produced as a secreted protein in baculovirus. For the expression in E. coli, the cDNA was cloned into the pET vector, and the rLep d 2 was produced with six C‐terminal histidine residues.The purified recombinant allergens were tested for immunoreactivity with 10 sera from subjects allergic to Lepidoglyphus destructor and were compared with native Lep d 2 using inhibition immunoblotting. The ability of the recombinant allergens to release histamine from basophils was evaluated using a histamine release assay.ResultsBoth expression systems produced immunoreactive recombinant allergens. They inhibited the binding of human sera to native Lep d 2 confirming their retained IgE binding properties. The yield of pure recombinant protein from the prokaryotic system was ≈ 1 mg/L compared to the eukaryotic system which produced up to 4 mg/L in an adherent cell culture system.ConclusionsWe have produced recombinant Lep d 2 in prokaryotic and eukaryotic expression systems which are comparable to the native allergen. Recombinant Lep d 2 might now be included in more extensive clinical studies to confirm its usefulness in the in vitro and the in vivo diagnosis of Lepidoglyphus destructor.
Indoor factors associated with concentrations of house dust mite allergen, Der p 1, in a random sample of houses in Norwich, UK
Authors: Luczynska  , Sterne  , Bond  , Azima  , Burney  
Published: March 2003

BackgroundStudies of house dust mite allergen concentrations suggest large variations both within and between homes. It is likely that different household characteristics influence allergen levels in different locations within the house.ObjectivesTo investigate household characteristics associated with higher concentrations of house dust mite allergen in a random sample of houses.MethodsInformation on indoor environment was obtained from 158 adults aged 20–44. Dust samples were collected from their living room floor, bedroom floor and mattress. Concentrations of Der p 1, the major allergen from the house dust mite Dermatophagoides pteronyssinus, were measured by monoclonal antibody immunoassay. Associations between mite allergen concentrations and household characteristics were examined using censored‐normal regression models. Factors that were related to Der p 1 (P ≤ 0.2) in univariate analyses were included in multivariable regression models.ResultsDer p 1 was not detected in any location in 10 (6.3%) houses. Geometric mean concentrations of Der p 1 were 1.9 μg/g in living room floor dust, 1.7 μg/g in bedroom floor dust and 2.0 μg/g in mattress dust. Approximately 25% of living room floor and mattress, and over 30% of bedroom floor samples had Der p 1 concentrations greater than 10 μg/g. Household characteristics associated with Der p 1 concentrations in both living room and bedroom were floor level, extractor fan in the kitchen, and age of carpet. Living room Der p 1 concentrations were also associated with gas oven/hob, window condensation, open fires, vacuum cleaner type, smokers in the house and age of house. Bedroom Der p 1 concentrations were also associated with use of blankets and wash temperature of bedding. Mattress Der p 1 concentrations were associated with window condensation, concrete bedroom floor and age of mattress.ConclusionDifferent household characteristics were associated with high Der p 1 concentrations in different parts of the house. These findings are relevant to design of allergen avoidance regimes or formulation of policy recommendations for reduction of disease associated with allergen exposure.
Adenoviral infection inhibits allergic airways inflammation in mice
Authors: STÄmpfli  , Ritz  , Neigh  , Sime  , Lei  , Xing  , Croitoru  , Jordana  
Published: March 2003

BackgroundRecent epidemiological studies have suggested that exposure to certain viruses and bacteria influences the development of allergy and allergic diseases, such as asthma. However, there is a paucity of experimental evidence examining the consequences of concurrent exposure to allergen and infectious agents, and the potential mechanisms by which allergic disease might be averted as a result.ObjectiveTo model this situation experimentally, we investigated whether a virally induced immune response, elicited by a replication‐deficient human type 5 adenovirus (RDA) administered at a site distant from the airways, could inhibit ovalbumin (OVA)‐induced airways eosinophilic inflammation.MethodsC57BL/6 mice were infected intramuscularly with RDA 16 h prior to intraperitoneal OVA sensitization. Cellular and cytokine responses in the lung/airways were examined after an OVA aerosol challenge.ResultsRDA infection significantly inhibited the inflammatory response in the lung tissue after antigen challenge. In the bronchoalveolar lavage (BAL), total cell number, eosinophils and lymphocytes were decreased by 70, 85 and 65%, respectively, after antigen challenge in RDA‐treated, compared with untreated, mice. RDA infection had no effect on IgE synthesis. The levels of IL‐5, IL‐4 and IFNγ in the BAL after antigen challenge were significantly lower in RDA‐treated mice. In vitro production of cytokines by splenocytes in response to OVA restimulation revealed a shift from IL‐4 in sensitized, PBS‐treated mice, to IFNγ in sensitized mice treated with RDA. Flow cytometric analysis revealed that RDA infection increased the proportion of CD8 T cells in the BAL; this change in T‐cell subsets was accompanied by an increase in both CD4 and CD8 T cells positive for intracellular IFNγ. Inhibition of antigen‐induced airways inflammation was IFNγ‐dependent but did not require IL‐12, as RDA‐treatment inhibited airways inflammation in IL‐12 but not IFNγ knock‐out mice.ConclusionThis study demonstrates that an immune response against a replication‐deficient adenovirus during the initial exposure to OVA inhibits the development of airways inflammation after antigen aerosol challenge.
Antihistamines in severe/chronic rhinitis
Authors: Bousquet  
Published: March 2003

Oral antihistamines generally represent the first line of treatment (after allergen avoidance) in mild seasonal allergic rhinitis (SAR), and in perennial allergic rhinitis (PAR) where symptoms are intermittent. They are safe, effective and easily administered. First‐generation antihistamines experienced problems mainly with sedation and anticholinergic activity. Second‐generation antihistamines are safer and have largely eliminated these effects, although a very small number of patients taking terfenadine or astemizole have developed a characteristic ventricular dysrhythmia, ‘torsade de pointes’. Ebastine is a potent second‐generation H1‐blocker that compares well with others in the class. It demonstrates no interaction with alcohol, does not induce sedation and has no clinically relevant effect on QTc interval at up to five times the maximum recommended dose. Ebastine acts rapidly to relieve symptoms of allergic rhinitis (including stuffiness) and has a long duration of action, allowing once‐daily dosing. Whilst comparable in efficacy to other second‐generation antihistamines at 10 mg, ebastine also has the advantage of flexible dosing. Thus, the lower dose of 10 mg is effective for treatment of mild SAR or PAR, and the dose can be increased to 20 mg once daily for control of patients with severe or chronic symptoms.
STAT6 deficiency in a mouse model of allergen‐induced airways inflammation abolishes eosinophilia but induces infiltration of CD8+ T cells
Authors: MIYATA  , MATSUYAMA  , KODAMA  , NISHIOKA  , KURIBAYASHI  , TAKEDA  , AKIRA  , SUGITA  
Published: March 2003

BackgroundThe TH2‐type cytokines have been reported to contribute to the asthmatic response. STAT6 has an essential role in IL‐4 signalling and in production of TH2 cytokines from T cells and is involved in IgE and IgG1 responses after nematode infections, indicating that STAT6 has an important role in allergic diseases.ObjectiveIn this study we investigated the effects of STAT6 deficiency on allergen‐induced airways inflammation in mice.MethodsBoth ovalbumin (OVA)‐sensitized STAT6 deficient (STAT6−/−) mice and wild‐type C57BL/6 mice were challenged with aerosolized OVA. Changes in inflammatory cell infiltration and cytokine levels in lung tissue as well as serum immunoglobulin levels were analysed in OVA‐challenged STAT6−/− and wild‐type mice.ResultsThe eosinophilia and lung damage normally resulting from aeroallergen challenge were not seen in STAT6−/− mice. Expression of TH2 cytokines (IL‐4 and IL‐5) in the lung tissue as well as IgE and IgG1 responses after OVA challenge were profoundly reduced in STAT6−/− mice, whereas expression of IFNγ was the same in STAT6−/− mice and wild‐type mice after OVA challenge. Immunocytochemical analysis of T cells showed the infiltration of CD4+ T cells but not CD8+ T cells increased into the lung of wild‐type mice after OVA challenge. However, the OVA‐exposed STAT6−/− mice demonstrated the infiltration of both CD4+ T cells and CD8+ T cells with a significant increase in percentage and total number of CD8+ T cells compared with OVA‐exposed wild‐type mice.ConclusionThese results indicate that factors which signal through STAT6 are important regulators of eosinophilia of allergic airway inflammation, regulating TH2‐type cytokine production both in CD4+ T cells and CD8+ T cells.
Nedocromil sodium eye drops are more effective than sodium cromoglycate eye drops for the long‐term management of vernal keratoconjunctivitis
Authors: VERIN  , DICKER  , MORTEMOUSQUE  
Published: March 2003

BackgroundVernal keratoconjunctivitis (VKC) is a severe though transient form of ocular allergy, predominant in young males, which requires careful management. Corticosteroids are effective but also cause serious topical side‐effects in the eye, such as glaucoma and cataracts. The safer, mast cell stabilizing anti‐inflammatories (commonly sodium cromoglycate) therefore have an important role. This parallel group study compared efficacy, tolerability and safety of sodium cromoglycate 2% with nedocromil sodium 2%, administered as one drop per eye four times daily for a period of 5 months.MethodsChildren aged 4–17 years, with a diagnosis of mostly limbal VKC in the last 12 months, entered a 2‐week baseline during which they used only artificial tears, and were then randomized to treatment, in groups of 18, on an investigator single‐masked basis. Daily symptom diary cards were kept by patients/guardians, and VKC was assessed by the clinician at approximately monthly intervals. Dexamethasone was provided for rescue control of severe symptoms, if needed.ResultsA total of 34 patients completed the study.Both trial treatments produced rapid improvements and many ocular signs and symptoms, including Trantas' dots, chemosis, itching, soreness and sticky discharge, were fully controlled by the end of the study. However, nedocromil sodium took effect more quickly, with a significant reduction compared to sodium cromoglycate for itching, grittiness, hyperaemia and keratitis within 6 weeks. In addition, nedocromil sodium was the more efficacious overall (significant vs sodium cromoglycate for hyperaemia, keratitis, papillae and pannus at 22 weeks). Both treatments were well tolerated and without serious adverse effects. Final opinions favoured nedocromil sodium, with full control of VKC recorded for 94% (patient opinion) and 100% (clinician opinion) of this treatment group, compared with 29% and 0%, respectively, in the sodium cromoglycate group.ConclusionsNedocromil sodium 2% eye drops is significantly more effective than sodium cromoglycate for treatment of VKC.
Allergen challenge primes for IL‐5 mRNA production and abrogates β‐adrenergic function in peripheral blood T lymphocytes from asthmatics
Authors: BORGER  , JONKER  , VELLENGA  , POSTMA  , DE MONCHY  , KAUFFMAN  
Published: March 2003

BackgroundIn previous studies, we have found a dysfunctional adenylyl cyclase (AC) system in patients with asthma after allergen provocation, which resulted in a 40–50% decreased generation of intracellular cAMP. In addition, in activated T helper lymphocyte clones, it has been demonstrated that IFN‐γ (TH1‐like cytokine) and IL‐5 (TH2‐like cytokine) are differentially regulated by the AC system. Therefore, we postulate that an increased IL‐5/IFN‐γ ratio as observed in asthmatics might be due to a dysfunctional AC system.ObjectiveTo assess whether a dysfunctional AC system as observed in asthmatics after allergen provocation, is responsible for an increased IL‐5/IFN‐γ cytokine ratio.MethodsPeripheral blood T lymphocytes of seven asthma patients were stimulated with anti‐CD3 plus anti‐CD28 MoAbs in the absence and presence of isoproterenol (ISO) and prostaglandin E2 (PGE2) to activate the AC system. Before, 3 h and 24 h after allergen provocation, IFN‐γ and IL‐5 mRNAs were detected by semiquantitative RT‐PCR.ResultsBefore allergen provocation, ISO (10−5 mol/L) significantly downregulated IFN‐γ mRNA (P < 0.03, n = 6), and showed a trend to upregulate IL‐5 mRNA (P = 0.138, n = 5). Three and 24 h after allergen provocation, ISO was not longer able to modulate IFN‐γ and IL‐5. In contrast with the observations with ISO, PGE2 still dose‐dependently inhibited IFN‐γ mRNA, both before, 3 h and 24 h after allergen provocation (n = 7). IL‐5 mRNA, but not IFN‐γ mRNA, was significantly upregulated in anti‐CD3 plus anti‐CD28‐activated T cells (P < 0.05, n = 5) 24 h after allergen provocation, compared with before allergen provocation.ConclusionTwenty‐four hours after allergen provocation, a significant reduction of β‐adrenergic control on IFN‐γ and IL‐5 mRNA expression was observed in peripheral blood T lymphocytes, which coincides with a selective priming of IL‐5 mRNA production.
Effects of exposure to gas cooking in childhood and adulthood on respiratory symptoms, allergic sensitization and lung function in young British adults
Authors: Moran  , Strachan  , Johnston  , Anderson  
Published: March 2003

BackgroundThere is evidence that people who use gas for cooking have reduced lung function and experience more respiratory symptoms than those who use other fuels for cooking.ObjectivesTo study the effect of the presence of a gas cooker in the home, during both childhood and adulthood, on respiratory symptoms, allergic sensitization and ventilatory function among young adults.MethodsA sample of 1449 young adults born in Britain 3–9 March 1958, who have been followed from birth to ages 7, 11, 16, 23 and 33 years, were examined at home at age 34–35 years. FEV1 and FVC were measured before and 20 min after inhalation of 400 μg salbutamol, and skin prick tests performed with three allergen extracts (grass, Der p 1 and cat). An interview on respiratory symptoms and indoor environmental exposures was included.ResultsNo association was found between gas cooking in childhood or adulthood and incidence or prognosis of asthma/wheeze, allergic sensitization or current severity of respiratory symptoms. Subjects who currently used gas for cooking had a significantly reduced FEV1 (– 70 mL, 95% CI ± 56) but not FVC (– 35 mL, 95% CI ± 61) compared with those who used electricity for cooking. This reduction in FEV1 was concentrated among men and current asthmatics.ConclusionThe use of gas for cooking is unlikely to be a major influence on respiratory morbidity in young adults.
Modified T‐cell activation pattern during specific immunotherapy (SIT) in cat‐allergic patients
Authors: MEISSNER  , KOCHS  , COUTELLE  , KUSSEBI  , BAUMGARTEN  , LØWENSTEIN  , KUNKEL  , RENZ  
Published: March 2003

ObjectiveThe aim of the study was to analyse early effects of specific immunotherapy (SIT) on immune functions in cat‐allergic patients.MethodsImmunological responses of peripheral blood mononuclear cells from eight cat‐allergic patients were analysed before and after SIT in comparison with 11 nonallergic controls. Cells were stimulated in vitro with either bacterial superantigen, mitogen, or cat allergen. Production of IL‐12 and TH1/TH2 cytokines was analysed by ELISA and lymphocyte subset distribution was assessed by flow‐cytometry.ResultsWe found a significantly reduced secretion of IL‐12 (P < 0.05) from cells of allergic individuals compared with the controls. This finding was associated with significantly lower IFN‐γ production after stimulation with allergen (P < 0.05) that did not increase during SIT. However, no significant differences were seen after stimulation with mitogen indicating an allergen specific IFN‐γ secretion response in allergic individuals. Prior to SIT IL‐5 production was significantly higher in cells of allergic donors stimulated with allergen < 0.005 or mitogen (< 0.05). After reaching the maintenance dose for SIT, allergen‐induced IL‐5 production returned to normal levels, whereas it remained elevated after stimulation with mitogen. These changes were associated with a reduced frequency of CD45 RO T cells following SIT.ConclusionThese results suggest that SIT exerts early effects on allergen‐specific T‐cell responses with selective inhibition of the up‐regulated TH2 immune response.