bluuebunny/crossref_metadata_2025_split huggingface dataset:
IFN‐γ is only partially restored by co‐stimulation with IL‐12, IL‐2, IL‐15, IL‐18 or engagement of CD28
Authors: Jung  , Witzak  , Dieckhoff  , Zachmann  , Heidrich  , Aversa  , Neumann  
Published: March 2003

BackgroundAlthough it is well established that T cells derived from patients with atopic diseases produce low levels of interferon‐gamma (IFN‐γ), the mechanisms responsible for this phenomenon are poorly understood.ObjectivesTo elucidate whether IFN‐γ production may be restored by co‐stimulatory molecules known to increase IFN‐γ production in vitro. Further, to investigate whether deficient IFN‐γ production is associated with disease activity.MethodsPurified peripheral T cells obtained from patients with severe atopic dermatitis (AD), individuals with a history but no symptoms of AD and healthy control subjects were activated with anti‐CD3 MoAbs in the presence or absence of anti‐CD28 MoAbs, interleukin (IL‐) 12, IL‐2, IL‐15 or IL‐18. IFN‐γ production was determined at the single cell level by flow cytometry, as well as by ELISA.ResultsActivated T cells from patients with severe AD produced less IFN‐γ than T cells from healthy control individuals. IL‐12 or engagement of CD28 enhanced IFN‐γ production in both healthy and atopic T cells. However, absolute values of IFN‐γ were still different. IL‐2, IL‐15 and IL‐18 did not restore IFN‐γ production. T cells from individuals with a history of AD produced more IFN‐γ than those from subjects with severe AD, but less than T cells from healthy individuals. Atopic T cells expressed regular levels of CD3, CD28 and Stat4, the main signal transducer and activator of transcription for IL‐12. IL‐4, IL‐10 and TGF‐β production by T cells were not different between healthy and atopic individuals.ConclusionIFN‐γ deficiency in atopic T cells is not due to a lack of responsiveness to CD28, IL‐12, IL‐2, IL‐15 or IL‐18. T cell‐derived cytokines able to antagonize IFN‐γ do not contribute to decreased IFN‐γ production. The extent of IFN‐γ deficiency seems to be dependent on disease activity.
IgE and T‐cell responses to high‐molecular weight allergens from bee venom
Authors: Kettner  , Henry  , Hughes  , Corradin  , Spertini  
Published: March 2003

BackgroundBee venom contains multiple allergens with a wide distribution of molecular weight. In contrast with conventional bee venom desensitization, peptide or recombinant allergen immunotherapy may have to take into account patients' individual patterns of humoral or cellular response.ObjectiveTo study immunoglobulin (Ig)E and T‐cell responses to high‐molecular weight bee venom allergens ≥ 50 kDa.MethodsBee venom proteins were separated by size exclusion chromatography and fractions were characterized by one and two‐dimensional gel electrophoresis. IgE antibody binding to bee venom fractions was analysed by immunoblotting and T‐cell responses by proliferation assay.ResultsAmong 38 bee venom‐hypersensitive patients, IgE recognition pattern of bee venom allergens varied greatly. IgE bound mainly to phospholipase A2 and furthermore to several proteins ≥ 50 kDa (50, 54, 69, 84 and 94 kDa). N‐terminal sequences of these proteins showed no homology with known proteins. In addition, peripheral mononuclear cells from patients as well as from nonatopic donors strongly proliferated in response to those proteins.ConclusionsAlthough present in low amounts, high‐molecular weight allergens from bee venom elicit strong IgE and T‐cell responses, and may need to be considered as clinically relevant. Therefore, the development of peptide or recombinant protein‐based immunotherapy for bee venom allergy may require careful characterization of such allergens.
Increased levels of IL‐5 positive peripheral blood eosinophils and lymphocytes in mild asthmatics after allergen inhalation provocation
Authors: HALLDÉN  , HELLMAN  , GRÖNNEBERG  , LUNDAHL  
Published: March 2003

BackgroundIn allergic inflammation eosinophils and TH2‐like lymphocytes are supposed to be the major effector cells and considered to contribute as cellular source of the key cytokine interleukin (IL)‐5.ObjectiveThe purpose of this study was to enable detection of IL‐5 containing leucocytes and to investigate whether the number of these cells in the blood circulation differed between healthy and asthmatics before and after allergen provocation.MethodsThe distribution of intracellular IL‐5 in human peripheral blood eosinophils (PBE) and lymphocytes (PBL) has been investigated using fixation and cell membrane permeabilization with octyl‐glucopyranoside, the FOG‐method, and flow cytometry. The intracellular staining was performed on leucocytes without any prior purification and in vitro stimulation. The specificity of IL‐5 binding to intracellular compartment of both PBE and PBL was confirmed by complete inhibition with human recombinant IL‐5.ResultsPreformed intracellular IL‐5 was detected in the main population of PBE (> 70%) in both healthy individuals and asymptomatic patients. Moreover, preformed intracellular IL‐5 was also detected in 4.8% and 2.4% of PBL from healthy individuals and asymptomatic patients, respectively. There was a correlation between the absolute number of PBE and IL‐5 positive PBE. In patients with pollen‐related asthma, the number of IL‐5 positive PBE and PBL increased significantly 24 h after an allergen inhalation provocation (P < 0.05). In the healthy control group no differences regarding IL‐5 positive PBE and PBL were obtained pre‐ and post‐allergen challenge.ConclusionsIn patients with mild allergic asthma, but not in healthy individuals, allergen provocation induces an increased absolute number of IL‐5 positive PBE and PBL. The reason for the relatively high number of IL‐5 positive PBL is unclear, but a plausible explanation might be that other lymphocyte subsets besides CD4+ TH2 can produce IL‐5. However, enumeration of IL‐5 positive leucocytes may be used as an activity marker and also be a useful tool in monitoring the inflammation in asthma.
Cord blood leucocytes/basophils produce and release sulfidoleucotrienes in response to allergen stimulation
Authors: Szépfalusi  , Todoran  , Elsässer  , Jagdt  , Wank  , Urbanek  
Published: March 2003

BackgroundLeucocyte‐derived sulfidoleucotrienes (SLT) from children and adults can be detected in vitro in response to specific allergen stimulation, a mechanism thought to require the presence of allergen‐specific immunoglobulin (Ig)E antibodies on the surface of basophils. It is unknown whether this mechanism is functional in cord blood basophils.ObjectiveWe studied the in vitro SLT‐release of leucocytes in response to allergen and anti‐IgE stimulation in term newborns and children with allergic diseases.MethodsCord blood from randomly selected term newborns were analysed for total IgE‐antibodies and in vitro SLT‐release in response to allergen and anti‐IgE stimulation. Children from an allergy outpatient clinic were used as the control group. The Cellular Allergen Stimulation Test (CAST) was used as read‐out system. Allergen stimulation was performed with an allergen‐mix containing 21 nutritive and inhalant allergens.ResultsPeripheral blood leucocytes/basophils derived from allergic children (n = 56; median SLT release 1049 pg/mL) were more responsive to anti‐IgE stimulation as cord blood leucocytes/basophils (n = 104; median 419 pg/mL P < 0.0001). In response to stimulation with an allergen‐mix, the two groups did not differ significantly from each other. Only SLT‐releasability in response to anti‐IgE showed a correlation with cord blood IgE.ConclusionsSulfidoleucotriene‐release of cord blood basophils is functional in response to allergens. It appears possible that cord blood basophils are armed with allergen‐specific IgE‐antibodies though not detectable in serum. Therefore, cord blood SLT‐release may indirectly reflect prenatal priming with allergens with subsequent production of allergen‐specific IgE.
VEGF levels in asthmatic airways do not correlate with plasma extravasation
Authors: Demoly  , Maly  , Mautino  , Grad  , Gougat  , Sahla  , Godard  , Bousquet  
Published: March 2003

BackgroundVascular permeability/vascular endothelial growth factor (VEGF) is a multifunctional cytokine which plays a role in chronic inflammation and angiogenesis. Its expression in bronchoalveolar lavage (BAL) has not been determined although VEGF may be relevant to the pathophysiology of asthma in which oedema is an important feature.MethodsWe studied VEGF, albumin and IgA immunoreactive levels in the BAL fluids obtained from 27 chronic stable asthmatics, nine untreated chronic bronchitis patients and 15 control subjects.ResultsBAL fluid levels of VEGF and VEGF normalized to IgA were not significantly different in any patient group. Both asthmatic steroid‐ and non‐steroid‐treated groups had significantly lower albumin levels in their BAL fluids explaining most of the 179% increased VEGF normalized to albumin ratios in non‐steroid treated asthmatics. Moreover, VEGF and albumin markers correlated in control subjects (r = 0.73, P = 0.006) and in chronic bronchitics (r = 0.75, P = 0.03, Spearman test), but not in asthmatics. VEGF was inversely correlated with asthma severity (GINA/NHLBI scores) in non‐steroid treated asthmatics (τ = − 0.52, P = 0.009, Kendall test).ConclusionsThus, the potential role of VEGF in asthma requires further studies on bronchial biopsies and induced sputum.
Immunocytochemical localization of cyclo‐oxygenase isoforms in cultured human airway structural cells
Authors: PETKOVA  , PANG  , RANGE  , HOLLAND  , KNOX  
Published: March 2003

BackgroundCyclo‐oxygenase (COX) exists as two isoforms, COX‐1, the constitutive isoform, and COX‐2, which is inducible by cytokines or inflammatory stimuli and may participate in airway inflammation.ObjectiveTo determine the basal distribution of COX isoforms, and their regulation by interleukin‐1 beta (IL‐1β), bradykinin (BK) and dexamethasone (Dex) in cultured airway structural cells.MethodsWe measured COX‐1 and COX‐2 in cultured human airway smooth muscle (HASM) cells, MRC5 fibroblasts and normal human epithelial cells (NHBE) using immunocytochemical analysis.ResultsThe majority of all types of untreated cultured cells expressed COX‐1 (75% of HASM, 75% of MRC5 fibroblasts and 72% of NHBE cells). Fibroblasts and smooth muscle cells showed low constitutive COX‐2 expression (2 and 8%, respectively) but this was higher in NHBE cells (28%). IL‐1β (24 h incubation) or BK (4 h incubation) had no effect on COX‐1 expression in any of the cells studied. In contrast, there was a two‐ and 1.5‐fold rise in the percentage of NHBE cells expressing COX‐2; a 7.5‐ and sixfold rise in the percentage of HASM cells expressing COX‐2 and a 33.5‐ and 20.5‐fold increase in the percentage of fibroblasts expressing COX‐2 after IL‐1β or BK treatment, respectively. Pretreatment with dexamethasone abolished IL‐1β‐ and BK‐stimulated COX‐2 induction in all cells studied.ConclusionCOX‐1 is expressed constitutively in human airway fibroblasts, smooth muscle and epithelial cells but epithelial cells also show constitutive expression of COX‐2. Both IL‐1β and BK induced COX‐2 expression in all cells studied and this induction was blocked by dexamethasone. Immunocytochemical techniques can be successfully used to detect the distribution of COX isoforms in cell cultures.
Mucosal immunity in extrinsic allergic alveolitis: salivary immunoglobulins and antibody against inhaled avian antigens among pigeon breeders
Authors: McSHARRY  , MacLEOD  , McGREGOR  , SPEEKENBRINK  , SRIRAM  , BOYD  , BOYD  
Published: March 2003

BackgroundInhaled antigens from pigeons can cause extrinsic allergic alveolitis (EAA); a model disease of pulmonary inflammation. Among pigeon breeders, serum antibody and sensitized lymphocytes specific for these antigens have been described primarily, but not always, with disease. Antibody activity within the lung may have a closer association with disease, however, sampling by alveolar lavage at bronchoscopy is impractical for screening, therefore we used saliva to quantify the mucosal antibody response.ObjectiveTo establish: (a) if antibody activity against inhaled avian antigens was detectable in the saliva of pigeon breeders, (b) if the distribution of saliva antibody and total immunoglobulin levels were quantitatively or qualitatively different from serum, and (c) whether the hypersensitivity symptoms of EAA were associated more with the mucosal or the systemic humoral immune response.MeasuresSaliva and serum total and avian antigen‐specific IgG, IgA (IgA1 and IgA2) antibody activity in 87 pigeon breeders and 24 control subjects with no avian exposure. Albumin levels were used as a protein reference and cotinine levels confirmed smoking status. Specific hypersensitivity symptoms and various exposure indices to pigeons were established by interview.ResultsAbsolute levels and relative proportions (vs albumin) of IgG, IgA and IgA1 in saliva, and IgG in serum, were significantly higher in pigeon breeders compared with controls, suggesting mucosal inflammation. Avian antigen‐specific antibody of all isotypes was readily demonstrable in saliva (predominantly IgA) and serum (predominantly IgG) from pigeon breeders, and there were no significant titres in controls. The levels of IgG antibody in saliva and in serum correlated significantly (r = 0.52, P < 0.001), and both correlated with the raised immunoglobulin levels. In both saliva and serum the IgG rather than the IgA antibody activity was associated with symptoms of EAA.ConclusionsAntibody activity in saliva and serum, representing the mucosal and systemic responses, respectively, were both strongly stimulated by inhaled antigens. The IgG antibody titres of saliva and serum correlated significantly and were a useful index of inflammation, as measured by the raised total immunoglobulin levels, and symptoms. This suggests that IgG antibody in serum may reflect clinical and immunological sensitization of the lung mucosa. Collecting saliva is noninvasive, and saliva antibody measurement is a convenient method for monitoring EAA, especially in children, and will facilitate sampling for example in epidemiological studies of antibody prevalence.
Subtribe‐specific monoclonal antibodies to Lolium perenne
Authors: LOVBORG  , BAKER  , TAYLOR  , YIN  , TOVEY  
Published: March 2003

Background and objectivesThe ability to measure personal exposure to airborne grass pollen is important in the understanding of allergic diseases. Visual identification is time consuming and it is difficult to distinguish between many grass pollens morphologically. Although grass pollens share common allergenic determinants, we attempted to produce monoclonal antibodies that would distinguish between species, tribes and subfamilies of grasses which would allow immunodetection of pollens.MethodsMonoclonal antibodies raised against Lolium perenne were screened for specificity against an extended panel of grass pollen extracts using standard ELISA techniques and a novel particle blotting assay using whole pollen grains.ResultsAntibodies showing specificity ranging from subfamily to part‐tribe specificity were raised. The most specific monoclonal antibodies (numbers 4, 13 and 17) had reactivity to Lolium perenne and Festuca elatior but displayed little cross‐reactivity to Phalaris arundinaceae and the rest of the Poeae tribe when tested by ELISA and no detectable cross‐reaction when tested with particle blotting.ConclusionMonoclonal antibodies that are functionally specific to only two grasses can be produced and used to discriminate between related grass species.
Protective effect of oral terfenadine and not inhaled ipratropium on adenosine 5′‐monophosphate‐induced bronchoconstriction in patients with COPD
Authors: Rutgers  , Koëter  , Van Der Mark  , Postma  
Published: March 2003

BackgroundInhalation of adenosine 5′‐monophosphate (AMP) causes bronchoconstriction in patients with asthma and in many patients with chronic obstructive pulmonary disease (COPD). In asthma, AMP‐induced bronchoconstriction has been shown to be determined mainly by release of mast cell mediators, and possibly by vagal nerve stimulation, since oral terfenadine (H1‐receptor antagonist) and inhaled ipratropium bromide (muscarinic receptor antagonist) both increase PC20AMP.ObjectiveTo investigate the mechanism of AMP‐induced bronchoconstriction in COPD.MethodsWe performed a randomized, double‐blind, placebo‐controlled, crossover trial. Forty‐four nonatopic hyperresponsive smokers with COPD (mean age ± sd: 60 ± 7 years, FEV1 61 ± 12% of predicted and FEV1/VC 51 ± 8%, geometric mean [GM] PC20methacholine 0.62 mg/mL and GM PC20AMP 6.77 mg/mL) participated. PC20methacholine and PC20AMP were assessed on 3 days. Before the challenges they used either 180 mg of oral terfenadine, 120 μg of inhaled ipratropium bromide, or placebo.ResultsGM PC20AMP was 5.44 mg/mL after placebo, increasing with 0.9 doubling concentration (P < 0.0001) after terfenadine and decreasing 0.3 doubling concentration after ipratropium bromide (NS). GM PC20methacholine was 0.75 mg/mL after placebo, increasing 0.4 doubling concentration after terfenadine (NS) and 3 doubling concentrations after ipratropium bromide (P < 0.0001).ConclusionThese findings indicate that histamine release is important in the pathophysiology of AMP‐induced bronchoconstriction in smokers with COPD, whereas vagal nerve stimulation does not play a role. Therefore, PC20AMP may be a valuable tool in evaluation of treatments which affect airway histamine release.
Amalgam allergy associated with exacerbation of aspirin‐intolerant asthma
Authors: Yoshida  , Mikami  , Nakagawa  , Hasegawa  , Onuma  , Ishizaki  , Shoji  , Amayasu  
Published: March 2003

BackgroundAspirin‐intolerant asthma can be induced not only by acidic analgesics (including acetylsalicylic acid), which effectively inhibit cyclo‐oxygenase, but also by cross‐reactivity with paraben, and other chemical additives.ObjectiveWe examined whether amalgam allergy is involved in the pathogenesis of a aspirin‐intolerant asthma.MethodsWe present the first case of aspirin‐intolerant asthma that improved after the removal of dental amalgam. In addition, we performed both the methacholine provocation testing and sulpyrine provocation testing before and after the removal of dental amalgam.ResultsIn addition, the methacholine concentration causing a 20% fall in FEV1 in provocation tests rose significantly, though hypersensitivity to analgesics evaluated with sulpyrine provocation testing did not decrease. These results suggest that amalgam sensitization is involved in bronchial hyperresponsiveness in aspirin‐intolerant asthma.ConclusionSensitivity to amalgam may cause exacerbation of aspirin‐intolerant asthma in some patients. To the best of our knowledge, this is the first case report of amalgam allergy associated with aspirin‐intolerant asthma.
The contribution of ‘holiday deaths’ to seasonal variations in asthma mortality in England and Wales
Authors: Nichols  , Hansell  , Strachan  
Published: March 2003

BackgroundIn younger age groups there is a summer peak in asthma deaths, but whether this is due to social or environmental factors is not known. One suggested social factor is a summer holiday away from home during which there may be a lack of compliance with medication or greater difficulty in getting medical help. In older age groups there is a winter peak in asthma deaths.ObjectiveTo study the contribution of ‘holiday deaths’ to seasonal variations in asthma mortality in England and Wales.MethodsRoutinely collected mortality statistics were used (all asthma deaths of persons dying in England and Wales, 1991–93 and 1995). Deaths occurring 40 miles or more from home were estimated using the District Health Authority in which the person was usually resident; the registration district of death; and the ‘transferability code’ (derived by the Office for National Statistics).ResultsThere were 484 asthma deaths in people aged 0–34 years, and 6337 asthma deaths in people aged 35 years or more. Deaths estimated to occur 40 miles or more from home contributed little (16%) to the summer peak in asthma deaths age 0–34 years, and nothing to the winter peak in asthma deaths age 35 years or more.ConclusionsHolidays away from home do not play an important part in explaining the seasonal variation of either young or old asthma deaths. Other social or environmental factors are more important.
Value of immunoglobulin E density in predicting nasal and bronchial response to inhaled allergens in rhinitic and asthmatic subjects with multiple sensitizations
Authors: Crimi E. , Voltolini S. , Minale P. , Falagiani P. 
Published: March 2003

BackgroundIn atopic subjects with multiple sensitizations to inhalant allergens the relationship between the specific serum immunoglobulin (Ig) E and the in vivo response to each allergen is not well established.ObjectiveTo investigate the relationship between the specific serum IgE expressed as amount (kU/L) or density (specific IgE/total IgE percentage) with the in vivo response to inhaled allergens in rhinitic and asthmatic subjects with multiple sensitization.MethodsBy means of Reverse Enzyme AllergoSorbent Test (REAST) the absolute values and the density of specific IgE for each sensitizing allergen was determined. Rhinitics (n = 12) underwent nasal and asthmatics (n = 11) bronchial allergen challenges with the two to three sensitizing allergens for a total of 33 nasal and 32 bronchial challenges. Correlations and degree of concordance between specific serum IgE and results of challenges were calculated.ResultsIgE density significantly correlated with nasal challenge score (rs = 0.72, P < 0.001), bronchial challenge score (rs = 0.56, P < 0.001) and late asthmatic response (rp = 0.53, P < 0.005). Among subjects with three sensitizations, comparison of values of IgE density with the results of challenges showed significant concordance in graduation (χ2 = 11.3, P < 0.005).ConclusionsIn subjects with multiple sensitizations, the nasal and bronchial response to the different sensitizing allergens may be predicted, at least in part, by the IgE density. A satisfactory agreement between graduation of the IgE density to the different allergens and the in vivo response to the same allergens has been found within subject.
Gaseous air pollution and atopy
Authors: Charpin  , Pascal  , Birnbaum  , Armengaud  , Sambuc  , Lanteaume  , Vervloet  
Published: March 2003

BackgroundPhotochemical air pollutants are commonly thought to be implicated in the gradual increase in the prevalence of atopy. However, no epidemiological data are available.MethodsTo clarify this issue, we performed a cross‐sectional epidemiological survey in 2604 primary school children, 10 and 11 years old, living in seven communities among which some have the highest photochemical exposure in France. The mean levels of the main gaseous air pollutants (SO2, NO2 and O3) were measured during a 2‐month period in 1993. The protocol included a standardized questionnaire, skin prick tests to common aeroallergens and in the atopic children, collection of a sample of mattress dust to measure group 1 mite allergens. Atopy was only defined on the basis of the skin prick tests.ResultsPercentage of positive skin tests and the number of positive skin tests were similar in the different communities looked at. The distribution of dust samples with a group 1 allergen level greater than 2 μg/g dust, was also similar. Logistic regression analysis including potential confounding factors, as well as the mean level of air pollutants, did not demonstrate any association between atopy and mean SO2, NO2 and O3 levels.ConclusionThe increase in photochemical air pollutants is unlikely to be a major determinant for the recent increase in the prevalence of atopy.