bluuebunny/crossref_metadata_2025 huggingface dataset:
Epicutaneous administration of hapten through patch application augments TH2 responses which can downregulate the elicitation of murine contact hypersensitivity
Authors: Wang  , Sun  , Wu  , Lin
Published: March 2003

Background and objective

Allergic contact dermatitis and its animal model, contact hypersensitivity (CHS), have long been documented as type 1 T‐cell‐predominant immune responses. Although type 1/type 2 T‐cell deviation has been repeatedly demonstrated to play an important role in many human diseases and their animal models, the potential of tilting type 1/type 2 T‐cell differentiation of CHS by modulating the manner of administration and dosage of hapten remains unexplored. This study examined the effect of these two factors on type 1/type 2 balance of CHS.

Methods

ELISA methods for detection of isotypes of hapten‐specific antibodies and cytokine profiles of in vitro reactivation culture as well as ear‐swelling assay were used to indicate type 1 or type 2 T‐cell immune responses.

Results

In this paper, it was demonstrated that dosage of hapten has no effect on the type 1/type 2 T‐cell balance of CHS, whereas epicutaneous administration of hapten through patch application could tilt the type 1/type 2 balance to decrease type 1 and to augment type 2 T‐cell responses. Patch application‐induced modulation is still effective in ever‐sensitized mice and the augmented type 2 T‐cell responses are persistent and increase progressively in strength after repeated immunizations. Moreover, it was demonstrated that the augmented type 2 T‐cell response can downregulate the elicitation of CHS. The major mediating cells of the enhanced type 2 T‐cell responses were determined to be CD4+ T cells (TH2 cells).

Conclusions

These data show that epicutaneous administration of hapten through patch application augments TH2 response which can downregulate the elicitation of murine CHS. This exploration may contribute to the understanding of regulatory mechanisms involved in contact allergy.
Does early exposure to cat or dog protect against later allergy development?
Authors: HESSELMAR  , Åberg  , Åberg  , ERIKSSON  , BJÖRKSTÉN
Published: March 2003

Background

It is unknown which factors in modern western society that have caused the current increase in prevalence of allergic diseases. Improved hygiene, smaller families, altered exposure to allergens have been suggested.

Objectives

To assess the relationship between exposure to pets in early life, family size, allergic manifestations and allergic sensitization at 7–9 and 12–13 years of age.

Methods

The prevalence of allergic diseases and various background factors were assessed in 1991 and 1996 by questionnaire studies. In 1991, the study comprised representative samples of children from the Göteborg area on the Swedish west coast (7 years old, n = 1649) and the inland town Kiruna in northern Sweden (7–9 years old, n = 832). In 1992, a validation interview and skin prick test (SPT) were performed in a stratified sub‐sample of 412 children. In 1996, this subgroup was followed up with identical questions about clinical symptoms as in 1991, detailed questions about early pet exposure were added and SPT performed.

Results

Children exposed to pets during the first year of life had a lower frequency of allergic rhinitis at 7–9 years of age and of asthma at 12–13 years. Children exposed to cat during the first year of life were less often SPT positive to cat at 12–13 years. The results were similar when those children were excluded, whose parents had actively decided against pet keeping during infancy because of allergy in the family. There was a negative correlation between the number of siblings and development of asthma and allergic rhinitis.

Conclusion

Pet exposure during the first year of life and increasing number of siblings were both associated with a lower prevalence of allergic rhinitis and asthma in school children.
A controlled study on the effectiveness of loratadine in combination with flunisolide in the treatment of nonallergic rhinitis with eosinophilia (NARES)
Authors: Purello‐D'Ambrosio  , Isola  , Ricciardi  , Gangemi  , Barresi  , Bagnato
Published: March 2003

Background

Nonallergic rhinitis with eosinophilia (NARES), accounting for some 15% of perennial rhinitis, is a nasal disorder whose main features are eosinophil counts in nasal smear higher than 10% and negative IgE tests. The mainstay of treatment is topical corticosteroids.

Objective

To evaluate the adjunctive effect of loratadine, a non‐sedating antihistamine with anti‐allergic activity, on nasal symptoms and eosinophil counts in nasal secretions in patients with NARES.

Methods

Thirty patients with NARES were divided in two groups, half receiving flunisolide two 25 μg puffs per nostril morning and night plus loratadine 10 mg u.i.d. and half the same doses of flunisolide plus placebo, according to a double‐blind fashion, for 3 weeks. The effectiveness of the treatment in the two groups was evaluated by comparing symptom scores and eosinophil counts, and safety was assessed by comparing the adverse effects.

Results

The loratadine treated group had better results both in nasal symptoms, with a decrease in sneezing (P < 0.000001) and rhinorrhoea (P < 0.006), respectively, corresponding with 73.4% and 66.7% with respect to 46.6% and 26.7% in the control group, and in eosinophil counts which decreased by 20% compared with 14.3% in patients treated with placebo and flunisolide. As to safety, only nasal irritation in two patients, one in each group, was reported.

Conclusion

Loratadine improves the effectiveness of flunisolide in treatment of NARES with no change in safety, and with no sedation.
Mechanisms of deficient interferon‐γ production in atopic diseases
Authors: JUNG  , MOESSNER  , DIECKHOFF  , HEIDRICH  , NEUMANN
Published: March 2003

Background

The mechanisms responsible for an imbalanced cytokine response in atopic diseases are still not understood. While impaired interferon‐gamma (IFN‐γ) production may be the result of a pathological T‐cell/antigen‐presenting cell (APC) interaction, evidence was provided that the T cell itself may have an intrinsic defect to produce IFN‐γ.

Objective

To clarify whether impaired IFN‐γ production by T cells from patients with atopic dermatitis (AD) represents an intrinsic defect in producing IFN‐γ.

Methods

Effector T cells were generated from CD4+ CD45RA+‐naive precursors from patients with AD and healthy control individuals by activation with anti‐CD3+ anti‐CD28 MoAbs. Following restimulation, IFN‐γ production was measured by ELISA and flow cytometry.

Results

IFN‐γ production by atopic T cells was decreased compared with healthy T cells. IL‐12 present at priming or high doses of IL‐2 during the culture period, even in the absence of IL‐12, completely restored IFN‐γ production. Conversion of naive CD45RA+ to CD45R0+ effector cells did not differ between atopic and healthy donors' T cells.

Conclusion

Impaired IFN‐γ production by T cells from atopic individuals is not the result of an intrinsic, genetically fixed, defect to produce sufficient amounts of IFN‐γ. The data provides evidence that correction of an impaired TH1 response in AD may be successful at the precursor T cell level.
Interleukin‐10 is localized to and released by human lung mast cells
Authors: Ishizuka  , Okayama  , Kobayashi  , Mori
Published: March 2003

Background

Mast cells control the local inflammation by producing many kinds of cytokines. Interleukin (IL)‐10 is one of the important cytokine that upregulate or downregulate inflammation.

Objective

The aim of this study is to ascertain whether IL‐10 is produced from human lung mast cells by cross‐linkage of high‐affinity Fcε receptors (FcεRI).

Methods

Mast cells were purified using affinity magnetic selection with mAb YB5.B8 (> 93% pure). Mast cells were precultured with human myeloma IgE (3 μg/mL) for 16 h and then washed, and stimulated with anti‐IgE in the presence or absence of recombinant human stem cell factor (rhSCF). We have studied the production of IL‐10 by using reverse transcription‐PCR, enzyme‐linked immunosorbent assay and immunocytochemistry.

Results

We found that human lung mast cells were immunocytochemically stained with anti‐IL‐10 mAb after IgE‐dependent stimulation. The activation of mast cells via FcεRI enhanced the intensity of the IL‐10 mRNA signal. Anti‐IgE (1 μg/mL) induced a median IL‐10 release of 301.7 (7.8–1532.4) pg/106 mast cells/24 h. In contrast, mast cells released only a small amount of IL‐10 in the absence of anti‐IgE. This difference was statistically significant (P = 0.02, n = 11).

Conclusion

Our findings indicate that human lung mast cells are capable of producing IL‐10 in response to IgE‐dependent stimulation.
Regulation of T‐helper cell responses to inhalant allergen during early childhood
Authors: Macaubas  , Sly  , Burton  , Tiller  , Yabuhara  , Holt  , Smallacombe  , Kendall  , Jenmalm  , Holt
Published: March 2003

Background

Recent evidence suggests that preschool children manifest patterns of allergen‐specific skin prick test (SPT) reactivity and in vitro T‐cell cytokine production which are similar to that of either atopic or nonatopic adults. However, published studies on this age group involve small sample sizes and a restricted number of cytokines, usually in response to polyclonal stimuli.

Objective

To elucidate the relationship between in vivo and in vitro immune responses to a major inhalant allergen house dust mite (HDM) in preschoolers.

Methods

Peripheral blood mononuclear cells (PBMCs) from matched groups of HDM–SPT+ and SPT− 6‐year‐olds (n = 30 and 29, respectively) tested for PBMC responses to HDM, and cytokine production measured at both the protein and mRNA levels. Immunoglobulin (Ig) E and IgG subclass antibody titres were determined in serum. Interrelationships between in vitro and in vivo HDM responses were examined via multivariate analyses.

Results

SPT reactivity to HDM was associated with in vitro production by putative T cells of interleukin (IL) ‐4, IL‐5, IL‐9, IL‐10, IL‐13 and low level IFNγ, and with production in vivo of IgE and (all) IgG subclass antibodies; HDM responses in the SPT− group were restricted mainly to IL‐10 and IFNγ and very low levels of IL‐4; IL‐6 production from non‐T‐cell sources was common. The cytokine most associated with positive SPT responses was IL‐9; SPT weal diameter correlated positively with IL‐4, IL‐5 and IL‐13 and negatively with IL‐10.

Conclusion

Detailed analysis of cytokine responses in this very young age group have the potential to uncover subtle relationships between in vivo and in vitro allergen reactivity which may be less clear in adults, in whom T‐cell response patterns are modified via chronic stimulation. The present findings which suggest potentially important roles for IL‐9 and IL‐10 in the early phase of allergic disease, may be one such example.
Interleukin‐5 enhances eosinophil adhesion to bronchial epithelial cells
Authors: Sanmugalingham  , De Vries  , Gauntlett  , Symon  , Bradding  , Wardlaw
Published: March 2003

Background

Eosinophil–bronchial epithelial cell interactions are thought to be central to the pathogenesis of asthma, both in terms of the epithelium as a source of pro‐inflammatory mediators and as a target for eosinophil‐mediated damage. We have therefore investigated adhesion interactions between these two cell types.

Objectives

To determine the role of eosinophil and epithelial activation on eosinophil adhesion to bronchial epithelium and to characterize the adhesion receptors mediating eosinophil adhesion.

Methods

Eosinophils were purified from human peripheral blood by immunomagnetic selection and adhesion to confluent cultures of the airway epithelial cell lines A549 and BEAS‐2B was studied.

Results

Stimulation of A549 cells with TNFα, IFNγ or a combination of 50 ng/mL of TNFα, IFNγ and IL‐1 (cytomix) did not effect eosinophil binding despite an increase in ICAM‐1 expression. Similarly stimulation of eosinophils with PAF or IL‐5 had no effect on eosinophil binding to medium‐ or cytokine‐treated A549 cells. In contrast stimulation of BEAS‐2B cells with cytomix caused a significant increase in eosinophil adhesion. This was associated with an increase in expression of ICAM‐1 and induced expression of VCAM‐1. Treatment of eosinophils with Mn2+ and IL‐5 but not eotaxin, RANTES or PAF also significantly enhanced eosinophil adhesion to medium‐treated BEAS‐2B cells. Using blocking mAbs we were able to demonstrate that the increased adhesion resulting from stimulation of eosinophils or BEAS‐2B cells was in both cases mediated by a combination of CD18 and α4 integrins.

Conclusions

This study demonstrates a selective role for IL‐5 in mediating integrin‐dependent eosinophil adhesion to airway epithelium and once again emphasizes the importance of this cytokine in controlling eosinophil activation in diseases such as asthma.
Serum immunoglobulin E levels predict human airway reactivity in vitro
Authors: Schmidt  , Watson  , Ruehlmann  , Magnussen  , Rabe
Published: March 2003

Background

Airway hyperresponsiveness to non‐specific stimuli is one characteristic feature of airway diseases such as bronchial asthma and chronic bronchitis. Until now, studies aiming to demonstrate a relationship between in vivo conditions associated with airway hyperreactivity and in vitro airway responsiveness have been inconclusive.

Objective

Since serum immunoglobulin (Ig) E is believed to be one determinant of airway reactivity in vivo, we studied whether in vitro airway reactivity in lung resection material from patients with elevated levels of serum IgE was increased as compared with patients with undetectable IgE. By this approach, we aimed to elucidate the role of circulating IgE for bronchial smooth muscle reactivity in vitro.

Methods

Bronchial rings from nine patients with total serum IgE levels above 200 U/mL and 10 patients with total serum IgE levels below 10 U/mL were passively sensitized, i.e. incubated overnight with buffer or sensitizing serum containing high levels of total IgE (> 250 U/mL). Afterwards, contractile responses to histamine were assessed in the organ bath.

Results

Histamine responsiveness was significantly increased in airways obtained from patients with IgE levels above 200 U/mL as compared with airways from patients with IgE levels below 10 U/mL (P < 0.05). Passive sensitization of bronchi from patients with low IgE significantly increased histamine responsiveness, as compared with non‐sensitized controls from the same patients (P < 0.05). In contrast, passive sensitization of airways from patients with elevated IgE did not further increase responsiveness. There was no difference in histamine reactivity between non‐passively sensitized and passively sensitized tissue preparations from patients with IgE above 200 U/mL and passively sensitized tissues from patients with IgE below 10 U/mL.

Conclusion

Our findings reveal that elevated levels of serum IgE predict airway hyperresponsiveness to histamine in vitro. At the same time, they indicate that the in vitro model of passive sensitization, in addition to its ability to induce allergen responses, also mimics conditions of non‐specific airway hyperreactivity, which are relevant under in vivo conditions.
Differences in size selective aerosol sampling for pollen allergen detection using high‐volume cascade impactors
Authors: Riediker  , Koller  , Monn
Published: March 2003

Background

Assessment of the allergen content of airborne particles small enough to reach the bronchiolar airways is important for a better understanding of allergic asthma.

Objective

In order to test the performance of a high‐volume cascade impactor for size‐selective sampling of airborne particles, the characteristics of pollen deposition, and the particle size‐dependent allergen distribution, were re‐examined.

Methods

Two cascade impactors with rectangular slots were run in parallel, one with glass fibre filters on all stages, the other with silicone grease on stage 2 (collection of particles of size 4.2–10.2 μm) instead. Pollen was counted using light microscopy and allergens were measured using ELISA techniques.

Results

In the impactor without the greased stage 2, a heavy bounce and blow‐off for pollen was found. Bounced pollen was deposited mainly on the back‐up filter, the sampling stage for particles smaller than 1.4 μm. However, if stage 2 was coated with silicone grease, less than 1% of total pollen was found in the lower stages. On the first stage of the sampler (50% cut‐point, 10.2 μm) where all pollen should impact, pollen had a deposition efficiency of only 24–47%, depending on the abundant pollen species. Much less allergen was found in fine particle fractions than in previous studies in which particles were sampled with similar samplers but without grease as a pollen trap.

Conclusions

The observed bounce and blow‐off of pollen without a greased stage 2 leads to serious mistakes when assessing the allergen content of the fractions collecting particles smaller than intact pollen, i.e., below 10.2 μm. Pollen allergen concentrations in respirable particle fractions are much lower than in the pollen size fraction. This is of great importance both for symptoms of sensitized allergic asthmatics and for research of asthma‐related mechanisms.
Farm environment in childhood prevents the development of allergies
Authors: Kilpeläinen  , Terho  , Helenius  , Koskenvuo
Published: March 2003

Background

A protective effect of infections in early life might explain the firmly reported finding of an inverse association between atopic disorders and large sibships.

Objective

To study the effect of childhood farm, rural non‐farm and urban environment, as well as family size and other factors on the occurrence of asthma, wheezing and atopic disorders up to young adulthood.

Methods

Data on lifetime prevalence of physician‐diagnosed asthma, allergic rhinitis and/or allergic conjunctivitis, atopic dermatitis, as well as self‐reported episodic wheezing from 10 667 Finnish first‐year university students aged 18–24 years were collected by a postal questionnaire. Associations of lifetime prevalence of the diseases with living on a farm, in a rural non‐farm and urban environment during childhood were estimated by logistic regression analysis. Adjustment was made for potential confounding by gender, parental atopy, parental education, number of older siblings, day care outside the home and passive smoking.

Results

The childhood farm environment independently reduced the risk for physician‐diagnosed allergic rhinitis and/or allergic conjunctivitis (adjusted odds ratio 0.63, 95% CI 0.50–0.79, P < 0.001), and for diagnosed asthma and episodic wheezing analysed together (OR 0.71, 95% CI 0.54–0.93, P < 0.05), but not for atopic dermatitis during lifetime. Urban childhood environment did not show independent increased risk when compared with rural non‐farm residence. The inverse association of sibship size with the occurrence of allergic rhinitis and/or allergic conjunctivitis was found among subjects with one (OR 0.86, 95% CI 0.77–0.96, P < 0.01) or at least four older siblings (OR 0.47, 95% CI 0.26–0.84, P < 0.05).

Conclusion

Childhood farm environment seems to have a protective effect against allergic rhinitis and/or conjunctivitis, and more weakly against asthma and wheezing irrespective of family size. Environmental exposure to immune modulating agents, such as environmental mycobacteria and actinomycetes, favouring manifestation of a nonatopic phenotype could explain the finding.
The role of CD23 on allergen‐induced IgE levels, pulmonary eosinophilia and bronchial hyperresponsiveness in mice
Authors: Riffo‐Vasquez  , Spina  , Thomas  , Gilbey  , Kemeny  , Page
Published: March 2003

Background

The role of Immunoglobulin (Ig)E in inflammation is the subject of considerable study and a number of studies have shown conflicting evidence for its role in eosinophil recruitment and bronchial hyperresponsiveness in a number of murine models. The low affinity IgE receptor, CD23, is known to act as a negative regulator of IgE production and we have used knockout mice deficient in CD23 to investigate the role of IgE in eosinophil recruitment and bronchial hyperresponsiveness in a murine model of airway inflammation.

Objective

To study the role of the low affinity FcεII receptor, CD23 in IgE production, lung inflammation and bronchial hyperresponsiveness.

Methods

Wild‐type and CD23 knockout C57Bl/6 mice (CD23−/−) were immunized by intraperitoneal injection with ovalbumin on days 0 and 14 and challenged with aerosolized antigen on day 21 for a period of up to 1 week. Blood samples, bronchoalveolar lavage and lung tissue samples were obtained to determine serum IgE levels and inflammatory cell numbers, respectively. Furthermore, airway resistance was measured to increasing concentrations of aerosolized 5‐hydroxytryptamine in order to evaluate the effect of CD23 deficiency on bronchial hyperresponsiveness to antigen challenge.

Results

Sensitization of wild‐type C57Bl/6 mice to ovalbumin resulted in elevated levels of total serum IgE and ovalbumin‐specific IgE, which was significantly augmented in CD23 knockout C57Bl/6 mice (CD23−/−). A significant increase in the percentage of eosinophils recovered in bronchoalveolar lavage fluid from wild‐type and CD23−/− mice was observed 24 h following 3 or 7 days aerosol exposure with ovalbumin (10 mg/mL). At 3 days, the increase in the percentage of eosinophils was significantly greater in CD23−/− groups. Immunohistochemical analysis of lungs sections revealed the presence of CD3+, CD4+ and CD23+ cells in wild‐type mice but a lack of immunofluorescence of CD23+ cells in CD23−/− mice. In wild‐type ovalbumin‐immunized mice, bronchial hyperresponsiveness to aerosolized 5‐hydroxytryptamine was observed following a 3‐day antigen challenge, which was significantly greater in CD23−/− ovalbumin‐immunized mice.

Conclusion

These studies demonstrate that CD23−/− mice have increased capacity to produce IgE consistent with the view of a negative feedback role for membrane‐bound CD23 and under such conditions, may account for the greater numbers of eosinophils recruited to the airways and bronchial hyperresponsiveness observed following acute but not chronic antigen challenge.
Skin prick test and serological analysis with recombinant group 2 allergens of the dust mites L. destructor and T. putrescentiae
Authors: Kronqvist  , Johansson  , Magnusson  , Olsson  , Eriksson  , Gafvelin  , Van Hage‐Hamsten
Published: March 2003

Background

The dust mites Lepidoglyphus destructor and Tyrophagus putrescentiae are important sources of allergen in farming environments. The major allergens of the dust mites L. destructor and T. putrescentiae have been cloned and expressed as recombinant proteins.

Objective

To evaluate the use of recombinant group 2 allergens of L. destructor (rLep d 2) and T. putrescentiae (rTyr p 2) in skin prick test (SPT), and serological analysis in sensitized and non‐sensitized farmers chronically exposed to dust mites.

Methods

Skin prick test with rLep d 2, rTyr p 2 and the corresponding commercial extracts was performed in 44 farmers sensitized to L. destructor and/or T. putrescentiae, and 38 control farmers. IgE and IgG subclass antibodies to the recombinant allergens were analysed by RAST and ELISA, respectively.

Results

Out of the 44 subjects positive in SPT to L. destructor and/or T. putrescentiae extract, 26 (59%) displayed a positive SPT to one or the other of the recombinant allergens, whereas 21 (48%) were positive to both. Significant correlations were registered between the sizes of the weals induced by rLep d 2 and rTyr p 2 and the corresponding RAST values (P < 0.001). A majority of subjects positive in SPT to the recombinant allergens had detectable IgG4 antibodies, and the levels were significantly higher in the dust mite sensitized group than in the controls (P < 0.05). No such differences were found in the IgG1values (P > 0.05). The results obtained with rLep d 2 and rTyr p 2 correlated relatively well with each other with respect to SPT, RAST and IgG4, suggesting that the allergens have similar or shared IgE epitopes. All the control subjects had a negative SPT and RAST to rLep d 2 and rTyr p 2.

Conclusion

Recombinant group 2 allergens from the dust mite L. destructor and T. putrescentiae represent useful tools for diagnosis of dust mite allergy.
Allergen‐induced airway inflammation and bronchial responsiveness in interleukin‐5 receptor α chain‐deficient mice
Authors: Tanaka  , Kawada  , Yamada  , Kawada  , Takatsu  , Nagai
Published: March 2003

Objective

The role of IL‐5 receptor α chain (IL‐5Rα) in the onset of bronchial hyperresponsiveness (BHR) to acetylcholine was investigated by testing IL‐5Rα knockout (IL‐5Rα KO) mice.

Methods

Mice were immunized with antigen at intervals of 12 days. Starting 10 days after the secondary immunization, mice were exposed to antigen three times every fourth day. Twenty‐four hours after the last antigen challenge, bronchial responsiveness to acetylcholine was measured and bronchoalveolar lavage was carried out.

Results

Twenty‐four hours after the last antigen inhalation, total and differential cells counts of bronchoalveolar lavage revealed a significant increase in eosinophils and lymphocytes in ovalbumin‐exposed wild‐type mice. In IL‐5Rα KO mice, there was little increase of eosinophils in bronchoalveolar lavage fluid (BALF). The production of IL‐5 in BALF increased in both mice after repeated antigen challenge, and there was no significant difference between wild‐type and IL‐5Rα KO mice. Similar to the BAL study, histological sections of lung tissue from ovalbumin‐exposed wild‐type mice exhibited airway eosinophilic inflammation, which was attenuated by the deficiency of IL‐5Rα chain. There was no significant difference in serum antigen‐specific IgE levels between wild‐type and IL‐5Rα KO mice after immunization nor antigen inhalation. Repeated antigen provocation caused BHR to acetylcholine in wild‐type mice. In contrast, no BHR was observed in IL‐5Rα KO mice after repeated inhalation of antigen.

Conclusion

These findings indicate that IL‐5Rα plays an important role in the development of antigen‐induced airway eosinophilia and BHR in mice.
Colonization with superantigen‐producing Staphylococcus aureus is associated with increased severity of atopic dermatitis
Authors: Zollner  , Wichelhaus  , Hartung  , Von Mallinckrodt  , Wagner  , Brade  , Kaufmann
Published: March 2003

Background

Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with colonization of the skin with Staphylococcus aureus known to produce toxins with superantigen (SAg) activity. Besides T‐cell activation these toxins induce T‐cell skin homing in vitro. This may contribute to the observed induction or enhancement of skin inflammation.

Objective

The aim of this study was to determine whether colonization with SAg‐producing S. aureus isolates modulates the intensity of AD. If so, it was of interest whether this may be primarily due to the toxins' effects as SAgs or as allergens.

Methods

In AD patients, healthy controls, and atopic controls SAg production by S. aureus isolated from skin or mucous membranes was investigated and correlated to the severity of the disease. Total IgE, SAg‐specific IgE, and T‐cell activation and recirculation markers were analysed and correlated with SAg production.

Results

Fifty‐seven percent of S. aureus strains isolated from AD patients produced SAgs. This frequency was higher compared to healthy controls (33%). SAg production by S. aureus was correlated with a significantly higher scoring of AD (SCORAD index, 58 ± 19 in SAg‐producing vs 41 ± 7 in non‐SAg‐producing germs; P < 0.05). However, the severity of the disease was not associated with sensitization against the SAgs staphylococcal enterotoxin A (SEA) and staphylococcal enterotoxin B (SEB). Furthermore, SAg production by S. aureus was inversely correlated with total IgE concentration (P < 0.05) and positively correlated with T‐cell activation (as measured by HLA‐DR and CD69 expression) and the expression of the T‐cell skin homing phenotype cutaneous lymphocyte‐associated antigen.

Conclusion

SAg production by S. aureus is suggested to be associated with an increased severity of atopic dermatitis. Since SAg production was found neither exclusively in AD patients nor in all patients, other pathogenic factors may be additionally effective.
Regulation of FcεRI expression on human monocytic cells by ligand and IL‐4
Authors: Reischl  , Dubois  , Peiritsch  , Brown  , Wheat  , Woisetschläger  , Mudde
Published: March 2003

Background

The FcεRI subunit composition and kinetic of expression differ between antigen‐presenting cells and mast cells. Up to now, there has been no human in vitro model available that mimics the characteristics on monocytes.

Objective

The characterization of a natural human monocytic cell line (THP1), which expresses FcεRI, and the comparison to primary human monocytes and other monocytic cell lines, which only express FcεRI after transfection with the human FcεRI α‐chain gene.

Methods

Surface receptor expression was characterized by flow cytometry, the human FcεRI α‐chain gene was introduced by electroporation, and induction of FcεRI α‐chain message was detected by semiquantitative RT PCR.

Results

Here we show that the parental human cell line THP1, but none of the other cell lines tested, displays surface FcεRI in response to IL‐4 or incubation with receptor ligand (IgE, antibody). Transfection of FcεRI α‐chain resulted in receptor expression on all cell lines, all of which increased surface FcεRI in the presence of IgE. Only the THP1‐α transfectant, however, further increased receptor levels in response to IL‐4, resulting from mRNA induction for the FcεRI‐α, but not the β‐ or γ‐subunit.

Conclusion

Based on THP1, U937 and HL60 and their α‐chain transfectants we present a model system for the study of FcεRI regulation and signalling on human cells. THP1 in particular, due to its responsiveness to both ligand and IL‐4, even without prior manipulation, is ideally suited to address questions on FcεRI modulation in an ‘allergic environment’.
Bronchial responsiveness to methacholine is increased in citrus red mite (Panonychus citri)‐sensitive children without asthmatic symptoms
Authors: Min  , Kim  , Park  , Lee  , Lee  , Son  , Kim  , Cho
Published: March 2003

Background

A recent investigation has suggested that citrus red mite (Panonychus citri, CRM) is a common sensitizing allergen among children living around citrus farms.

Objective

A cross‐sectional survey was performed to evaluate the bronchial responsiveness to methacholine in CRM‐sensitive children without asthmatic symptoms.

Subjects and methods

A total of 375 children living around citrus farms were enrolled in this study. There were 201 boys and 174 girls with a mean age of 12.5 (range 7–16) years. Each subject was evaluated by a questionnaire, a skin prick test with 13 common inhalant allergens including CRM, and a methacholine bronchial provocation test (MBPT).

Results

Positive rate of MBPT (PC20‐methacholine < 25 mg/mL) was higher in atopic rhinitic and atopic control children than in nonatopic rhinitic and nonatopic control subjects (41.3% and 33.3% vs 17.2% and 15.4%, respectively, both P < 0.05). Slope of dose–response curve (DRS, %/mg/mL) was higher in atopic rhinitic children than in nonatopic rhinitic, atopic control and nonatopic control subjects (14.3 ± 0.87 vs 9.4 ± 0.72, 10.0 ± 1.37 and 9.2 ± 1.51, P < 0.05, respectively). Both the positive rate of MBPT and the DRS were increased in children with positive skin response to CRM than in those without sensitization (48.2% vs 22.9%, P = 0.0001; 15.6 ± 1.26 vs 10.2 ± 0.65, P = 0.0001).

Conclusion

Bronchial responsiveness is increased in citrus red mite‐sensitive children even if they have no asthmatic symptoms.
Anaphylaxis to camomile: clinical features and allergen cross‐reactivity
Authors: Reider N. , Sepp N. , Fritsch P. , Weinlich G. , Jensen‐Jarolim E.
Published: March 2003

Background

Medicinal remedies of plant origin became very popular in recent years, and allergic reactions to these are on the rise, accordingly. Camomile has been reported as a potential trigger of severe anaphylaxis. The allergens responsible for camomile allergy have not been characterized as yet.

Objective

The present study aims at reviewing the clinical symptomatology of immediate‐type reactions in a series of patients sensitized to camomile and at characterizing the responsible allergens.

Methods

Fourteen patients with a history of allergy either to camomile or to spices or weeds, and a positive skin prick test/RAST to camomile were investigated for related allergic reactions to food, pollen and others. IgE‐binding patterns were determined by immunoblotting, inhibition tests and deglycosylation experiments.

Results

Ten of 14 patients had a clinical history of immediate‐type reactions to camomile, in some cases life threatening. Eleven subjects were also sensitized to mugwort in prick or RAST, eight to birch tree pollen. Using a polyclonal rabbit anti‐Bet v 1 antibody, a homologue of the major birch pollen allergen Bet v 1 was detected in two camomile blots. In four cases a group of higher molecular weight allergens (23–50 kDa) showed IgE‐binding to camomile. All allergens proved heat stable. Binding was inhibited in variable degrees by extracts from celery roots, anize seeds and pollen from mugwort, birch and timothy grass. Deglycosylation experiments proved the presence of carbohydrate determinants in camomile which were not responsible for IgE‐binding, though. Profilins (Bet v 2) were not detected in our camomile extracts.

Conclusion

Incidence and risk of type I allergy to camomile may be underestimated. Concurrent sensitization to mugwort and birch pollen is not infrequent. Bet v 1 and noncarbohydrate higher molecular weight proteins were found to be eliciting allergens and are responsible for cross‐reactivity with other foods and pollen.
Affinity of IgE antibody to antigen influences allergen‐induced histamine release
Authors: Mita H. , Yasueda H. , Akiyama K.
Published: March 2003

Background

Although affinity of an antibody for an antigen is recognized to be an important factor in determining its biological effects, little is known about the relevance of such affinity of IgE antibodies to the functional response.

Objectives

To investigate the effect of IgE antibody affinity to Der p 2 on Der p 2‐induced histamine release from human basophils.

Methods

The most probable value of the dissociation constant (Kd) of IgE antibody to Der p 2 was calculated and histamine release by Der p 2‐challenged leucocytes was used to evaluate the biological efficacy of the IgE antibody.

Results

The most probable Kd value of IgE antibody to Der p 2 ranged from 5.6 to 177.8 pM in 14 asthmatic patients sensitive to Der p 2. A significant correlation was observed in Der p 2‐induced histamine release between the sensitivity and the Kd value for Der p 2‐specific IgE antibody (rs = 0.797, P = 0.0040), suggesting that the higher the affinity, the lower the amount of allergen required for the release of a specific level of histamine.

Conclusion

Apart from the changes associated with the reactivity, the sensitivity of histamine release is closely related to the affinity of IgE antibody for its antigen.
Lack of allergic cross‐reactivity to cephalosporins among patients allergic to penicillins
Authors: Novalbos A. , Sastre J. , Cuesta J. , De Las Heras M. , Lluch‐Bernal M. , Bombín C. , Quirce S.
Published: March 2003

There are some contradicting data about clinical allergic cross‐reactivity to cephalosporins among patients who have had a previous allergic reaction to penicillins.

The purpose of this study was to assess the safety of administering cephalosporins to penicillin‐allergic patients.

The diagnosis of penicillin allergy was made by positive skin tests to penicillin reagents and/or provocation tests with the penicillin suspected of causing the allergic reaction. To assess the clinical tolerance to cephalosporins, 41 well‐characterized penicillin allergic patients diagnosed by positive skin tests and/or provocation tests were challenged with three cephalosporins that do not share the same side chain to the penicillin that induced the reactions: cephazoline, cefuroxime and ceftriaxone.

Skin prick and intradermal tests with all cephalosporins tested were negative. All penicillin‐allergic patients tolerated therapeutic doses of the three cephalosporins tested (cephazoline, cefuroxime and ceftriaxone) without any ill effect.

These results indicate that the risk of suffering from an allergic reaction on administering cephalosporins to penicillin‐allergic patients seems to be very low, provided that cephalosporins with a different side chain to the penicillin responsible for the allergic reaction are used.
Expression of costimulatory CD80/CD86‐CD28/CD152 molecules in nasal mucosa of patients with perennial allergic rhinitis
Authors: Hattori H. , Okano M. , Yoshino T. , Akagi T. , Nakayama E. , Saito C. , Satoskar A. R. , Ogawa T. , Azuma M. , Nishizaki K.
Published: March 2003

Background B7 molecules (CD80, CD86) and their counter‐receptors, CD28 and CD152 (CTLA‐4), play an important role in T cell‐mediated immune responses. We previously demonstrated that B7 molecules are selectively up‐regulated not only on B cells but also on T cells from the peripheral blood mononuclear cells of patients with perennial rhinitis cultured with allergen. However, the expression of CD80/CD86 molecules and their counter‐receptors in nasal mucosa, the actual inflammatory site of allergic rhinitis, has not yet been clarified.

Patients and methods Inferior turbinates from patients with either allergy to house dust or non‐allergic rhinitis were excised and immunohistologically stained. In addition, the inferior turbinates were challenged with paper discs containing extracts of house dust and subsequently excised. Samples were double stained with immunofluorescent‐labelled antibody to identify cells bearing CD86.

Results Without the nasal provocation, only the expression of CD86 was increased in nasal mucosa of patients with allergic rhinitis compared with those with non‐allergic rhinitis. However, following the nasal provocation with house dust, not only CD86, but also CD80, CD28, and CD152 were significantly expressed in allergic patients. Immunofluorescent double staining revealed CD86 expression in CD19, CD1a, CD14 and CD3 lymphocytes.

Conclusion These results indicate that the expression of CD80/CD86 molecules and their counter‐receptors is induced in allergic patients following nasal provocation with allergen, suggesting a local amplification of allergen‐specific immune responses in perennial rhinitis.
Benefits of high altitude allergen avoidance in atopic adolescents with moderate to severe asthma, over and above treatment with high dose inhaled steroids
Authors: Grootendorst D. C. , Dahlén S‐E. , Van Den Bos J. W. , Duiverman E. J. , Veselic‐Charvat M. , Vrijlandt E. J. L. E. , O'Sullivan S. , Kumlin M. , Sterk P. J. , Roldaan A. C.
Published: March 2003

Some patients with severe asthma cannot be controlled with high doses of inhaled steroids (ICS), which may be related to ongoing environmental allergen exposure.

We investigated whether 10 weeks of high altitude allergen avoidance leads to sustained benefits regarding clinical and inflammatory markers of disease control in adolescents with persistent asthma despite treatment with high dose ICS.

Eighteen atopic asthmatic adolescents (12–18 yr, 500–2000 µg ICS daily) with established house dust mite allergy, participated in a parallel‐group study. Quality of life (PAQL), lung function, bronchial hyperresponsiveness (BHR) to adenosine and histamine, induced sputum and urine samples were collected repeatedly from 10 patients during a 10‐week admission period to the Swiss Alps (alt. 1560 m) and at 6 weeks after return to sea level. Results were compared with those in eight patients, studied in their home environment at sea level for a similar time period. Throughout the study, asthma medication remained unchanged in both groups.

During admission to high altitude, PAQL, lung function, BHR to adenosine and histamine, and urinary levels of eosinophil protein X (U‐EPX), leukotriene E4 (U‐LTE4) and 9α11β prostaglandin F2 (U‐9α11β PGF2) improved significantly (P < 0.05), with a similar tendency for sputum eosinophils (P < 0.07). Furthermore, the changes in PAQL and BHR to adenosine and histamine were greater in the altitude than in the control group (P < 0.05). At 6 weeks after renewed allergen exposure at sea level, the improvements in PAQL (P < 0.05), BHR to adenosine (P < 0.07) and histamine (P < 0.05), as well as U‐EPX (P < 0.05) and U‐LTE4 (P < 0.05) were maintained.

A short period of high altitude allergen avoidance, on top of regular treatment with ICS and long‐acting β2‐agonists, results in improvement of asthma, as assessed by clinical and inflammatory markers of disease severity. These findings indicate that short‐term, rigorous allergen avoidance can improve the long‐term control of severe asthma over and above what can be achieved even by high doses of inhaled steroids.
Assessment of oxidant stress in allergic asthma by measurement of the major urinary metabolite of F2‐isoprostane, 15‐F2t‐IsoP (8‐iso‐PGF2α)
Authors: Dworski R. , Jackson Roberts Ii L. , Murray J. J. , Morrow J. D. , Hartert T. V. , Sheller J. R.
Published: March 2003

Asthma is a chronic inflammatory disease of the airways which may involve an oxidant injury to the lung. Assessment of oxidant stress is difficult in vivo, but measurement of F2‐isoprostanes (F2‐IsoPs), free radical‐catalysed products of arachidonic acid, appears to offer a reliable approach for quantitative measurement of oxidative stress status in vivo. We have recently developed a mass spectrometric assay for 2,3‐dinor‐5,6‐dihydro‐15‐F2t‐IsoP (15‐F2t‐IsoP‐M), the major urinary metabolite of the F2‐IsoP, 15‐F2t‐IsoP (8‐iso‐PGF2a). Measurement of the urinary excretion of this metabolite offers a reliable index of oxidative stress status in vivo that has advantages over measuring unmetabolized F2‐IsoPs in urine and plasma.

To assess the occurrence of oxidative stress in patients with atopic asthma following allergen exposure in vivo by measuring the urinary excretion of 15‐F2t‐IsoP‐M.

Analysis of 15‐F2t‐IsoP‐M by GC‐NICI‐MS in nine mild atopic asthmatics following inhaled allergen provocation and four asthmatic subjects after inhaled challenge with methacholine.

Urinary excretion of 15‐F2t‐IsoP‐M increased at 2 h after allergen challenge and remained significantly elevated in all urine collections during the subsequent 8‐h period of the study compared to the baseline value (anova, and Student–Newman–Keuls multiple comparisons test). No increase in the urinary excretion of 15‐F2t‐IsoP‐M occurred after inhalation of methacholine.

Allergen challenge causes an oxidant injury in human atopic asthmatics. 15‐F2t‐IsoP‐M is a valuable marker of oxidant stress in vivo.
Differential role of CD80 and CD86 on alveolar macrophages in the presentation of allergen to T lymphocytes in asthma
Authors: Balbo P. , Silvestri M. , Rossi G. A. , Crimi E. , Burastero S. E.
Published: March 2003

In the asthmatic lung the altered expression of costimulatory molecules (CD80, CD86) by alveolar macrophages contributes to T lymphocyte activation and expansion. We hypothesized that CD80 and CD86 on alveolar macrophages could differentially support allergic inflammation in adult asthma. Here we studied 11 subjects with mild allergic asthma and 11 atopic non‐asthmatics as controls. Dermatophagoides‐specific T cell lines were derived from peripheral blood from each subject. Bronchoalveolar lavage with evaluation of lung inflammatory cells was performed in all individuals at baseline and 24 h after allergen challenge. The expression of CD80 and CD86 costimulatory molecules by alveolar macrophages was studied and, in parallel, the efficiency of antigen presentation was measured in terms of IL‐4 and IL‐5 production by allergen‐stimulated autologous T cells. We found that in asthmatic subjects (i) the percent of CD80+, but not CD86+ alveolar macrophages was increased at baseline and did not change following allergen challenge; (ii) CD86, but not CD80, membrane expression was up‐regulated following allergen challenge; (iii) both CD80 and CD86 were required to support Th2 cytokine production by allergen‐specific T cells, with a prevalent role of CD86 after allergen challenge. Our data indicate that alveolar macrophages deliver costimulatory signals via CD80 and CD86, which support the production of Th2 cytokines by allergen‐specific T cells. They also indicate that CD86 in vivo is up‐regulated in the 24 h following allergen exposure and that this modulation is functionally relevant.
Neutrophils enhance eosinophil migration across monolayers of lung epithelial cells
Authors: Zuurbier A. E. M. , Liu L. , Mul F. P. J. , Verhoeven A. J. , Knol E. F. , Roos D.
Published: March 2003

During the late‐phase asthmatic response eosinophils and neutrophils infiltrate the lungs and cause severe damage. In this study, we investigated in vitro the migration of eosinophils, in the absence and presence of neutrophils, across a monolayer of lung H292 epithelial cells. The migration of eosinophils towards the complement fragment 5a (C5a) was increased when neutrophils were added to the upper compartment of the Transwells, and decreased when neutrophils were added to the lower compartment. Moreover, neutrophils exclusively stimulated eosinophil migration towards C5a, and not towards other chemoattractants such as RANTES, IL‐8 or PAF. Neutrophils and eosinophils differed in that neutrophils, but not eosinophils, rapidly inactivated C5a, suggesting that neutrophils in the upper compartment remove part of the active C5a that has diffused into the upper compartment. Indeed, we found that the addition of other C5a‐degrading agents, such as human serum or carboxypeptidase B, also enhanced eosinophil migration when added to the upper compartment and decreased migration when added to the lower compartment. Taken together, these results indicate that the presence of neutrophils influences the migratory behaviour of eosinophils in vitro. The neutrophils presumably maintain a proper C5a chemotactic gradient in the transmigration model, which results in enhanced eosinophil chemotaxis.