bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum IgE level is negatively correlated with the ability of peripheral mononuclear cells to produce interferon gamma (IFNγ): evidence of reduced expression of IFNγ mRNA in atopic patients
Authors: Teramoto  , Fukao  , Tashita  , Inoue  , Kaneko  , Takemura  , Kondo
Published: March 2003

Background

In patients with atopic diseases such as bronchial asthma and atopic dermatitis, an elevated serum IgE level is common. Several studies showed that interleukin‐4 (IL‐4) and interferon‐gamma (IFNγ) are important for regulation of IgE production.

Objectives

The study was designed to examine the pathogenesis of an elevated serum IgE level at the production levels of TH1‐type and TH2‐type cytokines.

Methods

The production of interleukin‐2 (IL‐2), IL‐4, interleukin‐5 (IL‐5) and IFNγ by peripheral blood mononuclear cells (PBMCs) stimulated with phytohemagglutinin (PHA) was analysed in 20 individuals with various serum IgE levels. The amount of IFNγ mRNA in the stimulated PBMCs was analysed using a quantitative polymerase chain reaction method.

Results

Cytokine production was analysed simply as a function of serum IgE level. The serum IgE level was negatively correlated with the amount of IFNγ secreted by PBMCs (n = 20, R = −0.724, P<0.005) when logarithmically transformed data were analysed, but were not or were only weakly correlated with those of IL‐4, IL‐2, or IL‐5 secreted by these cells (n = 20). For investigation of the cause of reduced IFNγ production in individuals whose serum IgE level are high, the amount of IFNγ mRNA was determined. The levels of IFNγ mRNA expression in the stimulated PBMCs correlated well with the amount of IFNγ secreted by the PBMCs (n = 8, R = 0.947, P < 0.001).

Conclusions

Reduced IFNγ production ability due to reduced IFNγ mRNA expression in PBMCs is associated with an elevated serum IgE level in atopic patients.
Differences in cellular infiltrates in the adenoid of allergic children compared with age‐ and gender‐matched controls
Authors: Fokkens W. J. , Vinke J. G. , De Jong S. S. , Bogaert D. P. V. D. , Kleinjan A. , Eichhorn E.
Published: March 2003

Background

Allergic sensitization of the airways occurs in the mucosa of the shock organ, or in the lymphatic stations draining these structures. The lymphatic structure closest to the nasal mucosa is the adenoid.

Objectives

The objective of this study was to find evidence for our hypothesis that allergic sensitization can occur in the adenoid. Of special interest, in this context are cell types involved in antigen‐allergen presentation (e.g. Langerhans cells) and effector cells of allergic disease.

Methods

In this study cellular infiltrates in adenoids of 16 allergic patients and 16 age‐and gender‐matched controls were evaluated. The number of cells positive for CD1a, CD4, CD8, CD‐68, chymase, tryptase, IgE, MBP and cells positive for interleukin (IL)‐4 were determined using immunohistochemical staining techniques. The epithelium, follicles and the interfollicular spaces were evaluated separately.

Results

When comparing the two groups a significant increase in cells positive for CD1a was found in interfollicular spaces of the allergic group (P = 0.008). CD1a+ cells in the follicular space and eosinophils in the interfollicular space showed a trend to be more numerous in the allergic group (P = 0.02 and P = 0.05, respectively). The other cell types investigated did not show significant differences between the groups.

Conclusions

The results of this study show for the first time that cells involved in allergic sensitization and allergic disease differ in the adenoid of allergic children compared with controls. These findings support our hypothesis that allergic sensitization takes place in the adenoid. Furthermore, this study confirms that CD1a+ (Langerhans) cells are involved in allergic disease.
Identification of volatile organic compounds emitted in the field by oilseed rape (Brassica napus ssp. oleifera) over the growing season
Authors: Mcewan  , Macfarlane Smith
Published: March 2003

Background

Oilseed rape has been associated by rural dwellers with seasonal symptoms, such as sneezing, coughing, headache and eye irritation, during its flowering season, for a number of years. This study was performed to identify the volatile chemicals emitted from oilseed rape in the field.

Objective

The objective of this study was to establish which volatile chemicals may be causative factors of oilseed rape allergy/toxicity.

Methods

The volatile organic compounds were sampled over the flowering period using a modified entrainment technique for headspace analysis under field conditions. These volatiles were then identified using thermal desorption‐gas chromatography‐mass spectrometry.

Results

The major constituents identified were the monoterpenes limonene, sabinene, β‐myrcene, and cis‐3‐hexen‐1‐ol acetate, a ‘green leaf’ volatile. The minor constituents included monoterpenes, sesquiterpenes, short chain aldehydes and ketones, other ‘green leaf’ volatiles and organic sulphides including the respiratory irritant, dimethyl disulphide.

Conclusions

This report highlights the diversity of volatile chemicals emitted by oilseed rape and confirms field emissions to be broadly similar to those found previously in laboratory studies. A review is carried out on the scientific literature already published on oilseed rape flower headspace analysis.
Oral sensitization to food proteins: a Brown Norway rat model
Authors: Knippels  , Penninks  , Spanhaak  , Houben
Published: March 2003

Background

Although several in vivo antigenicity assays using parenteral immunization are operational, no adequate enteral sensitization models are available to study food allergy and allergenicity of food proteins.

Objective

This paper describes the development of an enteral model for food allergy research in the Brown Norway (BN) rat.

Methods

The animals were exposed to ovalbumin either ad libitum via the drinking water (0.002 to 20 mg/mL) continuously for 6 weeks or by gavage (1 mg/mL per rat). Gavage dosing was performed either daily, twice a week, once a week or once every 2 weeks during a period of 6 weeks. No adjuvants were used during the sensitization studies.

Results

After intra‐gastric administration of ovalbumin once or twice a week or once every two weeks, no or only a very low frequency of ovalbumin‐specific antibody responses were detected. Daily intra‐gastric dosing with ovalbumin resulted in antigen‐specific IgG as well as IgE responses in almost all animals tested. Upon ad libitum exposure, ovalbumin‐specific IgG but no ovalbumin‐specific IgE was detected. The cellular response was examined by determination of delayed‐type hypersensitivity (DTH) reactions in the animals dosed by daily gavage and in the ad libitum exposed rats. Both sensitization protocols sensitized for DTH. The response was most pronounced in ad libitum exposed rats at day 28 of exposure.

Conclusions

These studies show that the BN rat may provide a suitable animal model for inducing specific IgG and IgE responses as well as specific T‐cell mediated hypersensitivity (DTH) to ovalbumin upon exposure via the enteral route without the use of adjuvants.
Histamine hypersensitivity induced by passive sensitization of human bronchus: effect of serum IgE depletion
Authors: Watson  , RÜhlmann  , Magnussen  , Rabe
Published: March 2003

Background

Sensitivity to specific allergens and increased sensitivity to common spasmogens are characteristic features of allergic asthma and are also features demonstrated by tissues passively sensitized with serum from atopic donors, displaying high levels of IgE. It is evident that the specific response to allergen is related to circulating levels of allergen‐specific IgE, but it is unclear whether the histamine hypersensitivity is also related to this immunoglobulin.

Objective

The objective was to deplete IgE in the serum of a donor with high levels of total and allergen‐specific IgE and compare specific‐allergen sensitivity and sensitivity to histamine in tissues passively sensitized with either the whole serum or the IgE‐depleted serum.

Methods

Serum from a Dermatophagoides farinae‐sensitive asthmatic (total IgE = 1047 U/mL, D. farinae‐specific IgE > 17.5 U/mL) was subjected to an immunomagnetic separation technique to reduce the levels of IgE (total and specific) to below 10 U/mL. Bronchial tissue from six non‐atopic donors was then passively sensitized overnight with either the whole serum or IgE‐depleted serum and D. farinae and histamine sensitivity were evaluated the next day using standard organ bath techniques.

Results

Passive sensitization with the whole serum resulted in the development of sensitivity to D. farinae and increased sensitivity to histamine (750 ± 169 mg contraction to 10 U/mL D. farinae, histamine pEC50 5.64 ± 0.16 and max. 813 ± 109 mg in sensitized vs 37 ± 34 mg contraction to 10 U/mL D. farinae histamine pEC50 5.05 ± 0.23 and max. 490 ± 84 in non‐sensitized tissues, P > 0.05). Incubation with IgE‐depleted serum still produced histamine hypersensitivity (histamine pEC50 5.57 ± 0.16 and max. 737 ± 70 mg P > 0.05), but no significant response to allergen was detected (20 ± 13 mg contraction to 10 U/mL D. farinae).

Conclusion

These results demonstrate, that increased reactivity to histamine and airway contraction to allergen induced by passive sensitization, occur through independent mechanisms and that, unlike allergen‐sensitivity, histamine hypersensitivity is caused by a serum factor other than IgE.
Activation of B‐lymphocytes during pollen season. Effect of immunotherapy
Authors: HÅkansson  , Heinrich  , Rak  , Venge
Published: March 2003

Background

B‐lymphocytes play an important part in the allergic reaction as producers of IgE antibodies.

Objective

To investigate the cell surface expression of the activation antigens CD23, CD40 and HLA‐DR on B‐lymphocytes in birch pollen allergic patients before and during birch pollen season and to study the effect of immunotherapy.

Methods

The study included 24 birch pollen allergic patients half of whom were treated with immunotherapy against birch pollen before the start of the season. Eleven of the 24 patients had asthma. Blood samples were taken and lung function was registered before the season began and before the immunotherapy treatment in January to February and during the season in May. The relative number of B‐lymphocytes (CD19+) of the lymphocyte population and the cell surface expression of CD23, CD40 and HLA‐DR on B‐lymphocytes was measured by the use of flow cytometry.

Results

In the control group of patients the relative number and concentration of B‐lymphocytes, the cell surface expression of CD23, CD40 and HLA‐DR on B cells, and the serum concentration of IgE increased during season compared with before season. In contrast, in the immunotherapy treated patients no changes in the number of B cells or cell surface expression of CD23, CD40 and HLA‐DR were demonstrated.

Conclusion

The elevated expression of CD23, CD40 and HLA‐DR on B cells, combined with increased levels of IgE in allergic patients during season could be explained by the effect of cytokines produced by activated TH2 cells. A shift from TH2 to TH1 cells might be the mechanism after the absence of signs of B‐cell activation in immunotherapy treated patients. The prevention of increased cell surface expression on B cells by immunotherapy may constitute a significant mechanism behind the beneficial effects of immunotherapy in the treatment of pollen atopy.
A comparative study of the tryptase release test and the cellular allergen stimulation test (CAST) in mite sensitive patients
Authors: Rossi  , Monasterolo  , Operti
Published: March 2003

Background

The stimulation of blood basophils to release mediators in vitro is widely used for diagnosis of allergic diseases. Tryptase release and sulphidopeptideleukotriene production are both triggered by cross‐bridging of adjacent IgE molecules on the surface of IgE‐bearing basophils.

Objective

We have compared the sensitivity of tryptase release test (TRT) and cellular allergen stimulation test (CAST) which, respectively, measure tryptase and sulphidopeptideleukotrienes that are produced upon cell stimulation by mite extracts.

Methods

Blood was taken from 247 patients with allergy to mites and 137 non‐allergic control subjects. We measured tryptase release from basophils after allergen challenge in vitro by sandwich radioimmunoassay. The sulphidopeptideleukotrienes production was quantified by an ELISA test based on a monoclonal antibody which recognized leukotriene T4 (LTC4) and its metabolites LTD4 and LTE4.

Results

Our data show that both methods are equally effective to distinguish allergic patients from normal controls (P > 0.0001). There was a significant correlation between mite‐specific serum IgE and CAST results (r = 0.69 for Dermatophagoides pteronyssinus; r = 0.73 for Dermatophagoides farinae). Correlations between IgE against mites and tryptase values appeared rather poor (r = 0.47 for Dermatophagoidespteronyssinus; 0.49 for Dermatophagoidesfarinae). Moreover, the data were used for the calculation of sensitivity, specificity, prevalence, and overall efficiency (Roc/Galen & Gambino analysis). The results were as follows: 71%, 87%, 64%, 76% (CAST results for Dermatophagoides farinae); 64%, 78%, 53%, 70% (TRT results for Dermatophagoides farinae).

Conclusion

The partial discrepancies observed could be interpreted as a consequence of conditions that were technically not optimal. False‐positive results may be due to the action of some non‐specific cytotoxic agent, false‐negative results may be due to hyporesponsive basophils or the low number of cells participating in the reaction and finally, in the case of TRT, to G4 monoclonal antibody to tryptase employed.
Cell lines of pulmonary and non‐pulmonary origin as tools to study the effects of house dust mite proteinases on the regulation of epithelial permeability
Authors: Winton  , Wan  , Cannell  , Gruenert  , J. Thompson  , Garrod  , Stewart  , Robinson
Published: March 2003

Background

Allergenic and non‐allergenic proteinases from house dust mites (HDM) cause loss of adhesion between airway epithelial cells that may result in a loss of functional cohesion between the cells and thus assist in allergen presentation. Improved cellular assay systems are needed to ascertain the mechanisms involved.

Objectives

To survey a series of epithelial cell lines (Calu‐3, 16HBE14o−, NCI‐H292 and A549 from human airways, and MDCK from dog kidney) and establish their utility for studies of the effects of HDM proteinases from D. pteronyssinus on epithelial permeability. To develop an improved method for measuring changes in epithelial permeability induced by HDM proteinases and other provocants.

Methods

The permeability of epithelial monolayer cultures to mannitol was calculated from measurements of clearance using a technique that permits mathematical estimation and reduction of non‐cellular diffusional constraints. Permeability was studied under control conditions and after perturbation of monolayers with HDM proteinases (separated into serine‐ and cysteine‐proteinase classes) or chelation of extracellular Ca2+. Fluorescent antibody staining was used to investigate whether the cells expressed tight junctions (staining of ZO‐1), desmosomes (staining of desmoplakin) and zonulae adherentes (staining of E‐cadherin).

Results

The Calu‐3 line was identified as an airway cell line that expressed functional tight junctions, desmosomes and zonulae adherentes. Calu‐3 monolayers exhibited a low clearance and permeability to mannitol, similar to that seen in the extensively characterized MDCK cell line. Clearance and permeability were significantly increased by treatment with either HDM proteinase fraction or by calcium chelation. 16HBE14o− cells also had a low permeability to mannitol under control conditions and expressed a similar repertoire of functional proteins from major intercellular junctions. In contrast, NCI‐H292 and A549 cell lines were functionally deficient in tight junctions, although they did express desmosomes and zonulae adherentes to a greater extent. Epithelial permeability was found to be a more appropriate and sensitive index of epithelial perturbation than was tracer clearance.

Conclusion

These results suggest that the Calu‐3 and 16HBE14o− cell lines are useful tools in studying the mechanism of HDM proteinases on airway epithelial cell function. HDM proteinases of both cysteine and serine mechanistic classes were found to perturb epithelial adhesion and function.
Inhibition of interleukin‐5 mediated eosinophil viability by fluticasone 17‐propionate: comparison with other glucocorticoids
Authors: Hagan  , Kita  , Gleich
Published: March 2003

Background

Inhaled glucocorticoids are commonly employed to treat patients with asthma. Eosinophils are important effector cells in the pathogenesis of asthma, and, in vitro, glucocorticoids modulate eosinophil viability.

Objective

Using this glucocorticoid inhibition of eosinophil viability, we compared the in vitro potencies of several inhaled glucocorticoids with particular attention to fluticasone 17‐propionate.

Methods

Eosinophils from normal or mildly atopic donors were purified, cultured with cytokines and glucocorticoids, and on day 4, after staining with propidium iodide, analysed by flow cytometry.

Results

Eosinophil viability was prolonged by interleukin (IL)‐5 in a concentration‐dependent manner; in contrast, dexamethasone inhibited the IL‐5 effect. Fluticasone 17‐propionate, 1.0–1000 nM, also inhibited the IL‐5 effect in a concentration‐dependent manner; interestingly, at 0.1 nM fluticasone 17‐propionate modestly, but significantly, enhanced eosinophil survival. High concentrations of IL‐5 and granulocyte‐macrophage colony‐stimulating factor essentially completely overcame the inhibitory effect of 1000 nM fluticasone 17‐propionate on eosinophil survival. In contrast, although interferon‐γ‐mediated eosinophil viability was inhibited by 1.0–1000 nM fluticasone 17‐propionate, this inhibition was not overcome by increased concentrations of interferon‐γ. Comparison of the glucocorticoid inhibition of eosinophil viability in the presence of 10 pg/mL IL‐5 resulted in these drug IC50 values (in nM): fluticasone 17‐propionate, 1.3; budesonide, 8.5; triamcinolone acetonide, 25; flunisolide, 32; dexamethasone, 94; beclomethasone 17‐monopropionate, 210; beclomethasone 17,21‐dipropionate, 290; and hydrocortisone, >1000.

Conclusion

Fluticasone 17‐propionate's effect on cytokine‐mediated eosinophil viability is similar qualitatively to other glucocorticoid preparations. However, quantitatively, fluticasone 17‐propionate has the most potent suppressive effects on IL‐5 mediated eosinophil viability among the currently available inhaled glucocorticoids in the United States.
Atopy and allergic disorders among adults in Tartu, Estonia compared with Uppsala, Sweden
Authors: JÕgi  , Janson  , BJÖrnsson  , Boman  , BJÖrkstÉN
Published: March 2003

Background

Recent studies in children and adults indicate that the prevalence of atopy and allergic disorders is lower in previously socialist countries in Eastern Europe compared with countries with a market economy while revealed risk factors are similar.

Objectives

To estimate the prevalence of atopy among adults in Tartu, Estonia and to compare the prevalence of risk factors for atopy and allergic respiratory diseases in Estonia and Sweden.

Methods

As a part of cross‐sectional study—European Community Respiratory Health Survey—random samples of 20–44 year olds (n = 351 in Tartu and n = 470 in Uppsala) and persons of the same age with asthma like symptoms or on current asthma medication according to a postal questionnaire (n = 95 in Tartu and n = 201 in Uppsala) were interviewed and circulating IgE antibodies were measured.

Results

The prevalence of atopy was 19% in Tartu and 32% in Uppsala (P < 0.001). The prevalence of sensitization to pollen was twice lower (11.5 vs 23.2; P < 0.001) and the prevalence of pollen associated asthma symptoms was four times lower (1.7 vs 6.8; P < 0.001) in Tartu than in Uppsala while sensitization to pollen was an equally large risk factor for asthma in both centres. Age was inversely related to cat and pollen associated symptoms of rhinoconjunctivitis in Uppsala (OR 0.6 and 0.7, respectively, P < 0.05) but not in Tartu.

Conclusions

The prevalence of atopy was lower in Tartu, Estonia than in Uppsala Sweden. Perception of allergic disorders seemed to be lower in Tartu than in Uppsala. Age did not influence the prevalence of atopy nor allergic disorders in Tartu, while in Uppsala age was inversely related to clinical allergy. This could suggest a cohort effect underlying the increasing prevalence of allergy in Western Europe.
The importance of serum IgE for level and longitudinal change in airways hyperresponsiveness in COPD
Authors: Renkema  , Kerstjens  , Schouten  , Vonk  , KOËter  , Postma
Published: March 2003

Background

Airways hyperresponsiveness (AHR) is an important feature of patients with chronic obstructive pulmonary disease (COPD). Little is known about factors that modulate AHR in COPD.

Objective

To study these factors, we performed a long‐term, double‐blind, parallel intervention study in 58 male, non‐allergic patients with COPD.

Methods

During a period of 2 years, patients were treated with inhaled budesonide (1600 μg/day), inhaled budesonide (1600 μg/day) plus oral prednisolone (5 mg/day), or placebo. PC20 histamine was measured at 4‐monthly intervals. The influence of treatment, smoking, age, level of lung function, initial serum IgE level and peripheral blood eosinophils on level and longitudinal change of PC20 histamine was analysed.

Results

During follow‐up, PC20 decreased in our group, and this decrease was not influenced by treatment. PC20 tended to decrease faster in current smokers than in ex‐smokers. PC20 was significantly associated with pre‐challenge FEV1 at each time point. Level nor decline of PC20 were significantly related to age. A higher initial serum IgE level was independently associated with a lower PC20. Moreover, a higher initial serum IgE level was associated with a slower annual decline of PC20, regardless of treatment, pre‐challenge FEV1, and other modulating factors. No significant associations were found between initial blood eosinophils and level or decline of PC20.

Conclusion

We conclude that AHR increases over time in non‐allergic patients with COPD. Treatment with an inhaled corticosteroid alone or in combination with oral prednisolone does not change this increase. Our study suggests an important role for IgE in the course of the disease, since a higher initial serum IgE level predicts a more favourable course with regard to annual decline of PC20 histamine.
Mechanical ventilation protects one‐storey single‐dwelling houses against increased air humidity, domestic mite allergens and indoor pollutants in a cold climatic region
Authors: Emenius  , Egmar  , Wickman
Published: March 2003

Background

Poor ventilation in modern, highly insulated housing is an important factor in promoting indoor humidity levels to exceed 7 g/kg in cold climatic regions.

Objective

To investigate the ventilation rate in houses with different ventilation systems in relation to indoor air humidity, domestic mite allergen levels and volatile organic compounds (VOC).

Methods

Measurements were performed regarding ventilation rate, indoor temperature, air humidity, mattress mite allergen concentrations using enzyme‐linked immunosorbent assay and total indoor VOC in 59 similarly constructed one‐storey single‐dwelling houses. In 22 of the houses, a mechanical supply and exhaust ventilation were installed after construction.

Results

In only five of the houses with mechanical supply and exhaust ventilation the air exchange rate per hour (ACH) was below 0.5 compared with 24 of the 29 houses with natural ventilation (OR = 0.06, CI 95% 0.01–0.2). None of the 23 houses with an ACH ≥ 0.5 had an absolute indoor humidity (AIH) of 7 g/kg air or more, compared with 10 of the 36 houses with an ACH < 0.5 (P = 0.01 ). In none of the 23 houses with an ACH ≥ 0.5 were concentrations of mite allergen exceeding 2 μg/g of dust found, compared with six of the 36 houses (17%) with an ACH below 0.5 (P = 0.04). Further, 10 of the 34 houses with a total VOC exceeding 200 μg/m3 had mite allergen in mattress dust exceeding 0.5 μg/g, compared with one of the 22 houses with VOC < 200 μg/m3 (P = 0.04).

Conclusion

The study shows that in modern, highly insulated, one‐storey single‐dwelling houses in cold temperate regions, mechanical ventilation increases the possibility of reaching an ACH of ≥ 5 which protects against indoor humidity levels contributing to mite survival as well as high levels of indoor air pollutants in winter.
Anaphylactic sensitization to aeroantigen during respiratory virus infection
Authors: O'donnell  , Openshaw
Published: March 2003

Background

Virus infections frequently exacerbate asthma, and in some cases may even precipitate its onset. Although this association is well known, experimental investigation has been hampered by the lack of adequate models.

Objective

The effects of acute respiratory virus infection on sensitization to aereoallergen were investigated in this study.

Methods

Nebulized ovalbumin was used as an aeroantigen in normal mice, and in those infected with respiratory syncytial virus or influenza A.

Results

Both viruses caused transient illness. Ovalbumin inhalation did not induce specific serum antibodies unless the mice were infected at the time of nebulization. In exposed uninfected mice cutaneous challenge with ovalbumin caused no response, but caused acute systemic illness and collapse if previous pulmonary exposure had occurred during respiratory infection. Mice that collapsed in response to cutaneous ovalbumin were found to have IgG1 specific to ovalbumin that was not found in the other mice. Intracellular cytokine staining of splenocyte cultures showed ovalbumin‐specific production of IL‐4 was enhanced by virus infection during exposure. In CD8+ T cells, ovalbumin‐specific interferon‐γ production was also enhanced by co‐infection with influenza. Both viruses were equally associated with the induction of anaphylaxis.

Conclusion

These results show that infection with respiratory viruses powerfully augments cellular and humoral immune responses to aeroantigen and provide an experimental model that allows such effects to be investigated.
Allergic rhinitis – making the correct diagnosis
Authors: Lund
Published: March 2003

The symptoms of rhinosinusitis occur in a variety of sinonasal conditions, which may be broadly classified as allergic (seasonal, perennial or occupational rhinitis/rhinosinusitis) or non‐allergic (caused by infection, or non‐infectious, e.g. drug‐induced or idiopathic). Correct diagnosis is important for optimal management. A thorough history should be taken, followed by general and endoscopic examinations and confirmatory investigations. Careful examination should reveal obvious alternative causes of symptoms, such as polyps or tumours. If allergy is suspected, this can be confirmed by further tests, particularly the skin‐prick test or measurements of serum specific IgE. Imaging techniques, usually X‐rays or CT scanning, are of use if a systemic condition or major sinonasal disorder needs to be excluded. Other useful diagnostic aids are measurements of nasal peak flow, rhinomanometry, acoustic rhinometry, olfactory threshold, and measures of mucociliary function (which may include biopsy for electron microscopy).
Environmental allergens and childhood asthma
Authors: Boner  , Bodini  , Piacentini
Published: March 2003

Exposure to allergens has been shown to lead to sensitization and to the subsequent development of airway hyperresponsiveness in genetically predisposed individuals. Increasing interest is being devoted to mechanisms for the prevention of allergen sensitization and asthma development. Primary prevention (avoiding the sensitization to allergens) requires a large effort as the majority of atopic sensitizations occur in children with no demonstrable risk at the birth. Secondary prevention (deterrence of disease expression despite prior IgE sensitization) requires methods for detecting the population at risk by means of large population screening. Tertiary prevention (minimizing the morbidity for those who already have the disease) may be achieved by allergen avoidance, which has been demonstrated to effectively decrease inflammation in symptomatic patients.
Tumour necrosis factor alpha (TNFα) in tears of atopic patients after conjunctival allergen challenge
Authors: VESALUOMA  , ROSENBERG  , TEPPO  , GRÖNHAGEN‐RISKA  , HAAHTELA  , TERVO
Published: March 2003

Background

Proinflammatory cytokines, such as TNFα are involved in the pathogenesis of allergic rhinitis and asthma.

Objective

Our aim was to study the tear fluid TNFα levels in atopic patients before and after topical ocular allergen challenge.

Methods

Thirteen patients were first challenged with topical allergen in the left eye and then dilution buffer in the right eye. Tear fluid samples were collected before the challenges and after 5, 30 and 60 min. Clinical symptoms were scored. Tear fluid TNFα concentrations were measured using a double‐antibody radioimmunoassay. TNFα release rates were calculated using the tear fluid flow in the collection capillary as an estimate for the tear secretion rate.

Results

The mean baseline TNFα concentrations (ng/L) were 1310 (allergen‐challenged eye) and 967 (control eye), and release rates (pg/min) 1.81 (allergen‐challenged eye) and 1.39 (control eye), respectively. In the allergen‐challenged eye, TNFα concentrations and release rates were 1479 and 4.30 (5 min), 1367 and 3.20 (30 min) and 1426 and 3.80 (60 min). In the control eye, TNFα concentrations and release rates were 746 and 0.67 (5 min), 1001 and 0.92 (30 min) and 1504 and 1.05 (60 min). The release rates of the allergen‐challenged eye were significantly increased at all time points after the challenge when compared with the baseline or the control eye.

Conclusion

Increased TNFα release rates suggest that this cytokine is an early mediator of allergy after conjunctival challenge.
The anti‐IgE/anti‐FcεRIα autoantibody network in allergic and autoimmune diseases
Authors: MARONE  , SPADARO  , PALUMBO  , CONDORELLI
Published: March 2003

Basophil granulocytes and tissue mast cells and their mediators play a role in the pathogenesis of several immune and inflammatory disorders. Human basophils and mast cells (FcεRI+ cells) can be activated through immunological interaction with the IgE‐FcεRI network. FcεRI+ cells can be triggered by cross‐linking between the Fab portions of IgE and multivalent antigens (direct anaphylaxis). ‘Reverse type’ anaphylaxis can occur through three distinct mechanisms: antibodies against the Fcε portion of IgE (anti‐IgE), antibodies against epitopes of the α chain of FcεRI (anti‐FcεRIα) and anti‐IgG acting on IgG–IgE complexes bound to FcεRI. Anti‐IgE autoantibodies are occasionally present even in normal donors and more frequently in a variety of allergic (chronic urticaria, atopic dermatitis and bronchial asthma) and autoimmune disorders (rheumatoid arthritis, lupus erythematosus and systemic sclerosis). IgG anti‐IgE from a small percentage of patients induces the release of mediators from human FcεRI+ cells. Some of the anti‐IgE autoantibodies present in allergic patients are non‐anaphylactogenic, thus representing a possible protective mechanism preventing the association of IgE with FcεRI. Anti‐FcεRIα autoantibodies also occur in a significant percentage of patients of chronic urticaria and probably non‐allergic asthma and some autoimmune diseases. Although anti‐IgE and anti‐FcεRIα autoantibodies, present in a percentage of patients with immune disorders, are relevant to the pathogenesis of these conditions, much remains to be learnt about their immunochemistry, their prevalence and precise role in various inflammatory diseases.
Cord blood‐derived human cultured mast cells produce transforming growth factor β1
Authors: KANBE  , KUROSAWA  , NAGATA  , SAITOH  , MIYACHI
Published: March 2003

Background

Mast cells frequently accumulate at the site of fibrosis and their contribution has been suspected in the pathogenesis of fibrotic conditions. However, it still remains unknown whether human mast cells synthesize transforming growth factor β1 (TGF‐β1).

Objective

We have investigated whether cord blood‐derived human cultured mast cells express messenger RNA (mRNA) for TGF‐β and produce bioactive TGF‐β1.

Methods

Mast cells were obtained by culturing mononuclear cells from cord blood in the presence of stem cell factor and interleukin‐6. Expression of mRNA for TGF‐β1 was examined by the method of reverse transcriptase‐polymerase chain reaction (RT‐PCR). Immunocytochemical staining for TGF‐β and growth‐inhibitory assay using Mv1Lu cells were also performed.

Results

The cultured human mast cells constitutively expressed mRNA for TGF‐β1. With calcium ionophore A23187, the intensity of the PCR‐amplified band for TGF‐β1 was not increased. Immunocytochemical staining showed that the cultured mast cells were positive for both latency‐associated peptide and activated forms of TGF‐β. Bioassay with Mv1Lu cells and R 4‐2 mutant cells showed that mast‐cell conditioned medium had a bioactivity of TGF‐β1.

Conclusion

Cord blood‐derived human cultured mast cells constitutively express mRNA for TGF‐β1 and produce functional TGF‐β1. Because TGF‐β1 has been shown to be highly fibrogenic, these results may highlight a novel role for human mast cells in tissue fibrosis.
The quantitative and qualitative defect of CD4+ CD45RO+ memory‐type T cells are involved in the abnormality of TH1 immunity in atopic dermatitis patients
Authors: MATSUYAMA  , URANO  , OHKIDO  , OZAWA  , OHTA  , KANEKO  , YAHATA  , TAKITA  , NISHIMURA
Published: March 2003

Peripheral blood mononuclear cells (PBMCs) obtained from atopic dermatitis (AD) patients produced low levels of IFN‐γ in response to Dermatophagoides farinae antigen (Der f Ag) plus IL‐2 or OKT3 MoAb in contrast with PBMCs obtained from healthy donors. The reduced IFN‐γ production in AD patients’ T cells appeared to be derived from the defect of CD4+ T cells but not CD8+ T cells. Indeed, from the cytoplasmic staining analysis of cytokines, it was demonstrated that the frequency of IFN‐γ producing CD4+ T cells (TH1 cells) in AD patients was markedly lower than that of healthy donors. From the phenotypic analysis using flow cytometry, it was also found that the number of CD4+ CD45RO+ memory type T cells was significantly reduced in AD patients compared with that of healthy donors. In addition to quantitative defect of memory type CD4+ T cells, functional defect of CD4+ CD45RO+ memory type T cells was also demonstrated in AD patients. Enriched CD4+ CD45RO+ T cells obtained from AD patients, who exhibited greatly reduced delayed‐type hypersensitibity (DTH) response in tuberculin test, showed no significant TH1 immunity in terms of IFN‐γ production by stimulation with OKT3 MoAb or purified protein derivative (PPD). Thus, the immunological abnortmality of TH1 immunity in AD patients appeared to be induced in concomitant with both the quantitative and qualitative defect of memory type CD4+ T cells.
Epidemiological study of the prevalence of allergic reactions to Hymenoptera in a rural population in the Mediterranean area
Authors: Fernandez  , Blanca  , Soriano  , Sanchez  , Juarez
Published: March 2003

Background

Systemic allergic reactions to Hymenoptera venom occur in a percentage that varies from 0.4 to 3.3%. Epidemiological studies indicate that from 15 to 25% of the general population can be sensitized to different Hymenoptera venom as well as the fact that the degree of exposure may be related to the prevalence found in those studies.

Objective

The objective of this study was to evaluate the prevalence of insect sting allergy and the venom sensitization in a rural population to three Hymenoptera previously found in the area: Polistes dominulus (Pd), Vespula germanica (Vg) and honey bee (Hb).

Methods

A rural community located in the south‐east of Spain, close to the Mediterranean Sea, was selected since the stinging Hymenoptera having been previously identified. A random sample of 310 subjects from the village census was studied. A questionnaire and a serum sample were obtained from every patient. The evaluation was conducted by a family doctor, who focused on the reactions to Hymenoptera sting, age, sex, occupation, atopia, previous Hymenoptera sting, stinging insect, interval to last sting and average stings per year. RAST to Hymenoptera venoms were also determined.

Results

The prevalence of systemic reactions was 2.3% (57.6% of them had a positive RAST). Large local reactions were found in 26.4% (only 28.5% of them had a positive RAST). Asymptomatic sensitization (positive RAST) was observed in 16.4% of subjects without reaction. Only a weak correlation between subjects with less than 3 years' interval to last sting exposure and positive RAST results was noted, whether they presented with a clinical reaction or not (P < 0.05).

Conclusions

The prevalence of systemic sting reactions in our rural community is higher than other general populations in the same Mediterranean area, and similar to other rural populations studied. The degree of exposure influences not only the prevalence found but also the detection of specific serum IgE.
Short‐term preseasonal birch pollen allergoid immunotherapy influences symptoms, specific nasal provocation and cytokine levels in nasal secretions, but not peripheral T‐cell responses, in patients with allergic rhinitis
Authors: Klimek  , Dormann  , Jarman  , Cromwell  , Riechelmann  , Reske‐Kunz
Published: March 2003

Backround

Birch pollen allergic rhinitis can be sufficiently treated with specific subcutaneous allergoid immunotherapy (IT). However, little is known about the clinical and immunological effects of short‐term therapy protocols.

Objective

To investigate the clinical efficacy of a birch pollen allergoid IT using seven preseasonal injections and to evaluate immunological parameters that might explain clinical findings.

Methods

Thirty‐seven patients were included into the study and randomized to either a symptomatic treatment or allergoid IT plus symptomatic treatment. Patients were examined during the pre‐IT season, at two extraseasonal visits both before and after IT and during the post‐IT season. At each visit, nasal secretion samples were taken and analysed for levels of IL‐4, IL‐5 and IFNγ. In addition, short‐term birch‐specific T‐cell lines (TCLs) were cultured from peripheral blood mononuclear cells of 10 patients of the IT group, both before and after IT, and the ratios of lymphocyte subpopulations were determined. Cytokine production by TCLs (IL‐4, IL‐5, IFNγ, IL‐10) and proliferation of TCLs in response to stimulation with birch pollen allergen were measured.

Results

It was possible to evaluate 27 patients in accordance with the study protocol. Clinical symptoms and medication intake were reduced as a result of the IT as were nasal secretion levels of IL‐5 (P = 0.007). IFNγ was increased in nasal secretions (P = 0.01), while IL‐4 was not measurable in most samples. No effect was found on proliferation of birch pollen‐reactive TCLs, cytokine production by TCLs and the frequency and ratio of CD4+ and CD8bright or CD45RA+ and CD45RO+ cells in peripheral blood (all P > 0.05). Conclusion Preseasonal IT with a birch pollen allergoid is clinically effective in allergic rhinitis and influences cytokine production in the nose, but does not modulate the measured responses of peripheral blood T cells.
Studies of differential gene expression in clinically derived eosinophil populations
Authors: Kilty I. C. , Vickers P. J.
Published: March 2003

Background

Influx of eosinophils into the post‐capillary bronchial epithelium and the subsequent release of inflammatory mediators is characteristic of the late phase of asthmatic attacks. The genes that serve to predispose the peripheral blood eosinophils of asthmatics to undergo this process are poorly defined. The aim of this report is to describe the differential gene expression of both the known pro‐inflammatory genes 5‐lipoxygenase and 5‐lipoxygenase‐activating protein (FLAP) and novel cDNA sequences in eosinophils derived from clinical samples.

Methods

Novel cDNA sequences representing genes upregulated in peripheral blood eosinophils of asthmatic as compared with nonasthmatic patients were identified by differential display polymerase chain reaction (DDPCR). The differential expression of these sequences, in addition to known pro‐inflammatory genes, were then studied by reverse dot blotting of amplified RNA generated from the eosinophils of nonasthmatic donors, asthmatic donors, asthmatic donors taking steroids, interleukin (IL) ‐3, IL‐5, granulocyte‐macrophage colony stimulating factor‐ (GM‐CSF) treated eosinophils from asthmatic donors and the eosinophilic cell line AML14.

Results

Four unique DDPCR‐generated 3′UTR DNA fragments were identified that showed differing patterns of expression between the eosinophil populations of interest. Expression of each of the novel clones was increased in the peripheral blood eosinophils of asthmatics and downregulated in those donors taking steroids. Expression of 5‐lipoxygenase was not found to vary between the different eosinophil populations, whereas FLAP was induced by treatment with the cytokine cocktail in both primary eosinophils and the eosinophilic cell line AML14.

Conclusion

The differential regulation of the novel cDNA sequences and FLAP in the range of eosinophil populations studied suggest that they may provide clinically relevant therapeutic targets. Moreover, the procedures used in these studies may provide a general approach to the study of differential gene expression in small numbers of cells such as those obtained from clinical samples.
The prevalence of immunoglobulin E antibodies to the proteins of rubber (Hevea brasiliensis) latex and grass (Phleumpratense) pollen in sera of British blood donors
Authors: Merrett  , Merrett  , Kekwick
Published: March 2003

Background

Although there have been many studies of the prevalence of latex allergy in populations deemed to be at risk, little is known of the potential allergic susceptibility to latex products prevailing in the general population.

Objective

To assess the possible prevalence of allergy to latex goods in a population of blood donors by measurement of specific antilatex immunoglobulin (Ig) E in blood, to relate this to prevalence of antigrass IgE in the blood donations, and to assess the prevalence of antibodies to grass, house dust mite and cat allergens in those donors having antilatex IgE antibodies.

Methods

Sera from two groups of donations obtained in the English West Midlands were assayed. A group of 2000 donations obtained in midwinter was assayed for antilatex and antigrass pollen IgE. A group of 5000 midsummer donations was assayed for total IgE, and antilatex IgE and the sera giving a positive reaction, assayed for antigrass pollen, antihouse dust mite and anticat IgE. The nature of the principal latex and grass pollen polypeptides reacting with IgE in the sera was assessed by immunoblotting.

Results

Anti‐latex IgE was detected in approximately 4% of the winter and 7% of the summer donations. The prevalence of antigrass IgE in the winter donations was approximately 20% and amongst the latex‐positive sera approximately 84% contained antigrass IgE. Of the summer donations of latex‐positive sera, 96% contained antigrass, 48.6% antimite IgE and 34% anticat IgE. The prevalence of both antilatex and antigrass IgE was age and sex related. Inhibition studies indicated cross‐reactivity of IgE with latex and grass pollen proteins.

Conclusions

Whilst 4–7% of the population may have serum IgE reacting with latex, the levels are low compared with those reacting with the aeroallergens studied. The apparent cross‐reactivity of some serum IgE with both latex and grass pollen taken with other evidence suggests that, in some individuals, allergy to latex may arise from an initial sensitization by grass pollen.
p38 MAP kinase regulates TNFα‐, IL‐1α‐ and PAF‐induced RANTES and GM‐CSF production by human bronchial epithelial cells
Authors: Hashimoto  , Matsumoto  , Gon  , Maruoka  , Kujime  , Hayashi  , Takeshita  , Horie
Published: March 2003

Background

RANTES and granulocyte macrophage‐colony stimulating factor (GM‐CSF) play an important role in the production of allergic inflammation of the airway through their chemotactic activity for eosinophils. Recent studies have indicated that p38 mitogen‐activated protein (MAP) kinase regulates cytokine expression in various cells; however, the role of p38 MAP kinase in RANTES and GM‐CSF production in human bronchial epithelial cells (BECs) has not yet been determined.

Objective

In the present study, we examined serine phosphorylation of MKK3 and MKK6 which is the upstream regulator of p38 MAP kinase and p38 MAP kinase activation in tumour necrosis factor (TNF)‐α, interleukin (IL)‐1α and platelet‐activating factor (PAF)‐stimulated BECs and the effect of SB 203580 as the specific inhibitor for p38 MAP kinase activity on RANTES and GM‐CSF expression in order to clarify the intracellular signal regulating RANTES and GM‐CSF production by human BECs.

Results

The results showed that TNFα, IL‐1α and PAF induced serine phosphorylation of MKK3 and MKK6, and p38 MAP kinase activation in BECs. SB 203580 inhibited p38 MAP kinase activity and RANTES and GM‐CSF production by TNFα‐, IL‐1α‐ or PAF‐stimulated human BECs.

Conclusions

These results indicate that p38 MAP kinase plays an important role in TNFα‐, IL‐1α‐ or PAF‐activated signalling pathway which regulates RANTES and GM‐CSF production by BECs and that the specific inhibitor for p38 MAP kinase activity might be useful for the treatment of allergic inflammation of the airway.
Interleukin‐13 and tumour necrosis factor‐α synergistically induce eotaxin production in human nasal fibroblasts
Authors: Terada  , Hamano  , Nomura  , Numata  , Hirai  , Nakajima  , Yamada  , Yoshie  , Ikeda‐Ito  , Konno
Published: March 2003

Background

There is increasing evidence that eotaxin is a key mediator in the development of tissue eosinophilia. However, the mechanism involved in the production of eotaxin has yet to be clarified. Most recently, it has been shown that interleukin (IL) ‐4 induces eotaxin in dermal fibroblasts. A novel cytokine termed IL‐13, which binds to the α‐chain of the IL‐4 receptor, shares many biological activities with IL‐4. It is known that fibroblasts express the IL‐4 receptor and produce collagen type I upon stimulation with IL‐4.

Objective

We investigated whether IL‐13, as well as IL‐4, are able to induce eotaxin production in human nasal mucosal fibroblasts (HNMFs). Furthermore, we investigated the effect of costimulation of IL‐13 and TNFα on eotaxin production.

Methods

HNMFs, isolated from inferior nasal mucosa samples, were stimulated by various kind of cytokines for 1–36 h at 37 °C in 5% CO2. The change in the expression of eotaxin mRNA was then evaluated by reverse transcriptase‐polymerase chain reaction and the Southern blot analysis. The amount of eotaxin in the culture media was measured by ELISA.

Results

IL‐13 as well as IL‐4 dose‐dependently induced eotaxin expression in HNMFs. Furthermore, IL‐13 and TNFα synergistically induced eotaxin expression in HNMFs, while they hardly induced eotaxin expression in endothelial cells, epithelial cells or eosinophils. The synergy was observed when pre‐incubation of HNMFs with IL‐13 was followed by a stimulation with TNFα, or HNMFs were simultaneously stimulated with IL‐13 and TNFα.

Conclusion

These results strongly indicate that IL‐13, as well as IL‐4, may be important in eotaxin‐mediated eosinophilic inflammation in nasal mucosa. In addition, in nasal mucosa, fibroblasts are the major cell source for eotaxin.