Dust Mite Antigen Research Articles

Serological responses to house dust mite antigens in atopic dogs while receiving allergen‐specific immunotherapy

In human atopic disease a beneficial response to immunotherapy may be associated with humeral changes in serum IgE and subclass IgG. The aim of this study was to investigate the humeral response to allergen‐specific immunotherapy (ASIT) in dogs with atopic dermatitis. Twelve dogs with clinical signs consistent with atopic dermatitis and positive intradermal test reactions to house dust mite antigens (Greer Laboratories, Lenoir NC, USA) were studied. The clinical response to ASIT (Greer) was evaluated when blood samples were collected at 0, 2 and 4 weeks; and at 3, 6 and 12 months after starting ASIT. The ASIT was administered for a minimum of 9 months. The serum concentration of total and subclass IgG antibodies was measured against Dermatophagoides farinae and Dermatophagoides pteronyssinus antigens (Greer) by ELISA using polyclonal and monoclonal antidog IgG reagents, respectively. Serum IgE was measured using a Fc‐epsilon R1 receptor alpha chain‐based ELISA. The data were analysed using a multilevel model in MLwiN software (Institute of Education, University of London, UK). Antibody concentrations of IgE and total IgG increased during the period of administration of ASIT and decreased after ASIT was stopped. There was no obvious pattern in subclass‐IgG concentrations during ASIT. Response to ASIT was excellent (four dogs), equivocal (three dogs) or poor (five dogs). During ASIT a poor or equivocal response was associated with a statistically significant increase in IgE to D. pteronyssinus antigen compared with the excellent responders. This relationship was present to a lesser extent with IgE to D. farinae and total IgG to both antigens. This study was supported, in part, by the RCVS Alison Alston Canine Award and by Heska Corporation.

T-cell clonotypes specific for Dermatophagoidespteronyssinus in the skin lesions of patients with atopic dermatitis

T-cell mediated immune response, toward the house dust mite (HDM) antigens in particular, has been reported to be involved in the pathogenesis of atopic dermatitis (AD). On the other hand, studies on the infiltrating lymphocytes in the skin lesion of AD revealed oligoclonal T-cell accumulation. However, it is not clear exactly what antigen(s) the accumulating T cells are exactly recognize in situ. Therefore, this study attempted to determine whether or not the clonally expanded T-cell clones in the diseased skin recognize HDM. Specifically, peripheral blood mononuclear cells (PBMC) obtained from six patients with AD, who revealed high titers of anti-HDM IgE, were stimulated with HDM antigens purified from Dermatophagoides pteronyssinus (Dp). T-cell clonotypes expanded by the stimulation were then identified by the analysis of their T-cell receptor (TCR) B-gene sequences using a combination of the reverse transcription–polymerase chain reaction and subsequent single strand conformation polymorphism separation. The Dp-responding T-cell clonotypes were compared with those that accumulated in the AD skin lesion in vivo. Nucleotide sequences of the TCR were also determined. As a result, the Dp stimulation induced oligoclonal T-cell expansion from the originally heterogeneous peripheral T-cell population of AD patients. However, only a small part of the Dp-reacting T-cell clonotypes detected in PBMC was identical to those accumulated in the AD skin lesion in vivo, and vice versa. This indicates that the frequency of the clonal expansion of Dp-specific T-cell clonotypes in the skin lesion of AD would be rather limited.

Lipoteichoic acid from Staphylococcus aureus induces Th2-prone dermatitis in mice sensitized percutaneously with an allergen.

We found previously that lipoteichoic acid (LTA) from Staphylococcus aureus has the ability to induce Th2 cytokine production by peripheral blood mononuclear cells (PBMC) from patients with atopic dermatitis (AD). However, it is not known whether LTA can induce a Th2-dominant cytokine response in the skin of AD patients. The purpose of this study was to determine the effects of LTA in mice sensitized percutaneously with a house dust mite antigen (MA) through barrier-disrupted skin, as an experimental animal model of AD. Mice were sensitized with MA by a single topical application to barrier-disrupted abdominal skin. Seven days after the sensitization, the mice were challenged on the dorsal skin by LTA to elicit localized skin inflammation. The cytokine response in the dorsal skin was investigated by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistological analysis. The infiltration of inflammatory cells in the skin was also observed by histological staining. Injection of LTA into the dorsal skin of MA-sensitized mice, which show a Th2-dominant cytokine response against the homologous antigen, increased the expression of mRNA for IFN-gamma, IL-4 and IL-5, but not IL-2. Immunohistological analysis demonstrated that levels of IFN-gamma, IL-4 and IL-5 transcripts corresponded with those of protein synthesis. In addition, the dorsal skin of MA-sensitized mice challenged with LTA showed significantly increased numbers of neutrophils, eosinophils, mononuclear cells and mast cells compared with control mice challenged with LTA. These results suggest that LTA has the ability to induce localized Th2-prone dermatitis in an allergen-independent manner in the skin of AD patients and may explain the role of colonization with S. aureus in AD patients.

Der f 16: a novel gelsolin-related molecule identified as an allergen from the house dust mite, Dermatophagoides farinae

Allergen from the house dust mite ( Dermatophagoides sp.) is a major trigger factor of allergic disorders, and its characterization is crucial for the development of specific diagnosis or immunotherapy. Here we report the identification of a novel dust mite ( Dermatophagoides farinae) antigen whose primary structure belongs to the gelsolin family, a group of actin cytoskeleton-regulatory proteins. Isolated mite cDNA, termed Der f 16, encodes 480 amino acids comprising a four-repeated gelsolin-like segmental structure, which is not seen in conventional gelsolin family members. Enzyme immunoassay indicated that recombinant Der f 16 protein, prepared using an Escherichia coli expression system, bound IgE from mite-allergic patients at 47% (8/17) frequency. This is the first evidence that the gelsolin family represents a new class of allergen recognizable by atopic patient IgE.

Tumor necrosis factor-alpha and interferon-gamma modulate in vitro expression of nitric oxide synthase in human nasal epithelial cells

Interest in the physiological, pathological and therapeutic implications of nitric oxide (NO) have grown exponentially, with human nasal cavity and paranasal sinuses considered a dominant source of NO, indicating that this molecule possesses the diversity of biological effects in the regulation of airway clearance and nonspecific cellular immunity. We previously observed differences in NO synthase (NOS) isoform constitutively expressed in nasal epithelial cells (NECs) from allergic and normal subjects. We extended the previous work to determine whether in vitro stimulation with proinflammatory cytokines influences levels of different NOS isoform expression. Nasal epithelial cells were sampled from the inferior turbinate in a group of 16 healthy normal controls and 11 patients with perennial allergic rhinitis against house dust (HD) mite antigen. 1 x 10(5) cells were incubated in conditioned medium for 24 hours. Human recombinant interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), or both (cytomix) were added to a final concentration of 10 ng/ml. Cells were then fixed with 4% paraformaldehyde and processed for fluorescence immunocytochemistry. Immunoreactivity for 2 NOS isoforms, inducible NOS (iNOS) and endothelial NOS (eNOS), was studied by laser scanning confocal microscopy and fluorescence intensity was assessed quantitatively. We observed constitutive eNOS expression in epithelial cells of all subjects. Different treatments with cytokines did not affect eNOS expression. Cytokine treatment, however, significantly augmented iNOS expression in the control group. The average increase induced with IFN-gamma, TNF-alpha, and cytomix was 1.8, 2.33, and 2.31-fold. Nasal epithelial cells in the HD group showed elevated steady-state iNOS expression even in untreated. Cytokine treatment did not affect the degree of iNOS expression in this group. These results confirm our previous findings that nasal epithelial cells in patients with allergic rhinitis produce higher levels of NO through the concomitant expression of different NOS isoforms. We also demonstrated that nasal epithelial cells have the potential to express iNOS protein spontaneously or upon stimulation with inflammatory cytokines, such as IFN-gamma and TNF-alpha. Because the high level of exhaled NO is considered a potential marker of allergic airway inflammation, preserving the iNOS gene from its unregulated induction may be important for maintenance of nasal homeostasis and may offer a tool for therapeutic intervention.

Impairment of skin prick test response to house dust mite antigens in schistosoma mansoni infected subjects highly exposed to house dust mite allergens

Impairment of skin prick test response to house dust mite antigens in schistosoma mansoni infected subjects highly exposed to house dust mite allergens

Effectiveness of Indoor Environment Management Education for Prevention of Allergic Asthma

Purpose. The objective of this research is to provide the indoor environment management education program for the asthma patients and their families and then analyze the effectiveness in education preventing allergic asthma. Methods. A pre-post single group quasi-experimental design was used to provide an education program about correct indoor environment management to a total of 58 households (29 patient households and 29 normal households). The performance rate of correct indoor environment management procedure, amount of house dust mite antigen, allergy subjective symptoms score and knowledge score about indoor environment management were compared before and after the education to test the effectiveness of the education.

Isolation of Human scFv Antibodies Specific for House Dust Mite Antigens from an Asthma Patient by Using a Phage Display Library

Background: In order to characterize human antibodies with specificity for mite allergens at the molecular level, a scFv phage display library was constructed using peripheral blood mononuclear lymphocytes from an asthma patient allergic to mite as Ig gene sources. Methods: Immunoglobulin VH and V gene fragments were obtained by polymerase chain reaction, and randomly combined in pCANTAB-5E vector. The resulting human scFv phage display library had 3×10 4 independent clones, and biopanning was performed with house dust mite extracts. Results: Four scFv clones specific for house dust mite extract were isolated. Immunoblot assay showed that our clones reacted to 25 kDa and 50 60 kDa proteins with unknown identity in mite extracts. Sequence analysis indicated that two clones (b7 and c15) are identical, and all clones belong to human VH3 subgroup. On the other hand, light chain usage was different in that two clones (a2 and b7/c15) belonging to Vκ4 subgroup, but a4 used Vκ1 light chain gene. Conclusion: Our approach should facilitate provision of useful information on the antibody responses against allergens at the molecular level in humans. (Immune Network 2002;2(2):91-95)

Childhood asthma in the United States: Urban issues

The prevalence and morbidity of asthma are growing problems that appear to affect urban populations and particularly impoverished centers disproportionately. Poor children are more likely to be hospitalized for asthma than nonpoor children, and are more likely to experience clinical and social dysfunction due to asthma. While guidelines exist for best care of childhood asthma, the neediest children are least likely to encounter the benefits of these recommendations. The relationship between host and environment in both primary causation and disease exacerbation is an area of research and debate. Allergen exposure in early life appears to correlate with sensitization and expression of atopy and asthma. Impoverished households are more likely to be reservoirs for dust mite and cockroach antigen in high concentrations than more affluent settings. Lifestyle factors, including diet and ambient air quality, may be disease modifiers. Suboptimal systems for delivery of healthcare to high-risk populations are obvious targets for blame. Poor children are more likely than nonpoor children to receive sick care in emergency rooms that lack a connection to chronic care providers. Besides the method of delivery, the quality of care is questionable, as poor children are less likely to receive the anti-inflammatory maintenance medications for asthma that evidence-based guidelines recommend. Efforts to correct these problems must take into account such issues as explaining the nature of the disease and the best intervention strategies to people who have a diverse array of cultural backgrounds, belief systems, and life stressors. Efforts to improve the status quo are underway in many communities. Environmental control measures to reduce dust mite and cockroach exposure have met with some success. Models to improve access to care and acceptance of care may improve community outreach maneuvers that connect the medical establishment with families and patients. Examination and assessment of new approaches to facilitate this sort of communication hold promise and are receiving attention as well as research dollars.

The ACVD task force on canine atopic dermatitis (IV): environmental allergens

Numerous environmental allergens have been incriminated in the pathogenesis of canine atopic dermatitis (AD). These include dust and storage mite antigens, house dust, pollens from grasses, trees and weeds, mould spores, epidermal antigens, insect antigens, and miscellaneous antigens such as kapok. In this paper, we review the literature concerning the allergens that have been reported to contribute to canine AD. We conclude that attempts to identify the relevant canine antigens in the past have been plagued by a lack of standardisation of extracts and techniques, and the presence of false-positive and -negative reactions in allergy tests. Until these problems are rectified, it is unlikely that we will be able to provide a list of major and minor antigens for dogs. Hence, we recommend that future studies should be aimed at determining the major patterns of reactivity and cross-reactivity to specific protein allergens within antigenic extracts using electrophoresis and immunoblotting techniques. Once this information becomes available, it may be possible to use a selection of genetically engineered, highly pure antigens for both diagnostic and therapeutic purposes in canine allergy investigations. The use of such antigens will allow standardisation of canine allergy testing and immunotherapy so that the reliability and efficacy of these procedures can be objectively assessed.

Allergen-induced generation of mediators in the mucosa.

The inhalation of antigens does not normally lead to allergic inflammation, but airway resident cells and their products may affect the outcome of antigen exposure. It is therefore important to elucidate how potential allergens interact with airway epithelial cells and other cells located within and below the epithelium. Some studies have indicated that certain antigens, particularly the major house dust mite antigen Der p1, penetrate the airway epithelium by intracellular transportation or paracellular passage, depending on their concentrations, time of exposure, and ability of the cells to inactivate them. If an antigen possesses proteolytic activity, such as Der p1, and it reaches high concentrations or the exposure is prolonged, the disruption of the tight junction can also favor the transepithelial passage of other antigens. In this way, the antigens can easily encounter the effector cells located between epithelial cells and below the basement membrane. The magnitude of this phenomenon may be more prominent in the airways of asthmatic patients, as their epithelium is more permeable to Der p1 than the epithelium of nonasthmatic patients and releases cytokines after exposure to very low concentrations of this antigen for brief periods. Epithelial cell activation may facilitate the development of allergic mucosal sensitization to Der p1 and contribute to the antigen-induced inflammatory response by affecting the migration and function of dendritic cells, mast cells, and eosinophils. Also, there might be a secondary release of interleukin-6 and endothelin-1, which can have a detrimental effect on the cardiovascular function.

House dust mite control measures for asthma.

The major allergen in house dust comes from mites. Chemical, physical and combined methods of reducing mite allergen levels are intended to reduce asthma symptoms in people who are sensitive to house dust mites. The objective of this review is to assess the effects of reducing exposure to house dust mite antigens in the homes of mite-sensitive asthmatics, assessing chemical and physical methods separately and together. We searched the Cochrane Airways Group trials register, checked reference lists of articles and hand-searched Respiration (1980 to 1996) and Clinical and Experimental Allergy (1980 to 1996). The Cochrane Library is searched every three months. Randomised trials of mite control measures vs placebo or no treatment in asthmatic people known to be sensitive to house dust mites. Two reviewers applied the trial inclusion criteria, assessed their quality and extracted the data independently. Study authors were contacted to clarify information. Twenty-nine trials (939 patients in the analyses) were included, with two trials awaiting assessment. Nine trials assessed chemical methods alone, 15 physical methods alone, and 5 a combination of chemical and physical methods. Overall, there was no statistically significant difference improvement of asthma (relative risk 1.04, 95% confidence interval 0.83 to 1.31), asthma symptom scores (standardised mean difference -0.07, 95% confidence interval -0.35 to 0.22), medication usage (standardised mean difference -0.14, 95% confidence interval -0.43 to 0.15), or peak flow in the morning (standardised mean difference 0.04, 95% confidence interval -0.13 to 0.21). For chemical methods used alone, there was a statistically significantly adverse effect on symptoms (P = 0.03), whereas for physical methods used alone as evaluated in parallel group trials, there was a statistically significant beneficial effect (P = 0.02). However, because of the large number of significance tests we performed, two significant results would be expected to occur by chance. Currently available evidence from controlled trials of chemical and physical approaches to reducing exposure to house dust mite antigens in the homes of mite-sensitive asthmatics does not provide a secure basis for advice and policy. Further trials - one of them very large - are currently in progress. The additional evidence from these studies will help to clarify whether or not the substantial efforts required to implement strategies intended to reduce mites can be expected to yield beneficial effects of a magnitude that people with mite sensitive asthma consider worthwhile.

Suppression of allergic immune responses to house dust mite (HDM) in rats exposed to 2,3,7,8-TCDD.

Exposure to various xenobiotics, including oxidant gases, diesel exhaust, and certain pesticides, has been reported to exacerbate pulmonary allergic hypersensitivity responses. Increased lymphocyte proliferative responses to parasite antigens or increased antibody responses to sheep erythrocyte have also been reported in rats exposed to TCDD before infection or immunization. As a result, these studies were conducted to test the hypothesis that TCDD exposure exacerbates the allergic response to house dust mite antigen. Brown Norway rats were injected, ip, with 0, 1, 10, or 30 microg TCDD/kg 7 days before intratracheal (it) sensitization to semipurified house dust mite allergen (HDM). Fourteen days later, rats were challenged with HDM and immediate bronchospasm was measured. At this time point, plus 2 and 7 days later, inflammatory cells in bronchoalveolar lavage fluid (BALF), HDM-specific IgE levels in serum, and HDM-driven cell proliferation in bronchial lymph nodes and spleen were evaluated. TCDD exposure decreased both immediate bronchoconstriction and specific IgE synthesis after the HDM challenge; 7 days later, HDM-specific IgE responses remained suppressed. Total serum IgE levels were similar in all groups. HDM challenge alone significantly increased cellular and biochemical indicators of lung injury, both of which were suppressed by TCDD exposure. The proliferative response of lymph node cells, but not of spleen cells, to HDM was also suppressed at the highest TCDD dose, although the splenic response to Concanavalin A was elevated. It appears that early events in the response to HDM are affected by TCDD exposure, since message for IL5 was dramatically reduced 2 days after sensitization, but not after challenge. We therefore conclude that TCDD exposure suppressed, rather than enhanced the development of allergic immune responses and the expression of immune-mediated lung disease.

Biphasic cytokine expression by T cell clones from patients with atopic dermatitis with different incubation periods and strengths of stimuli.

It has been proposed that T helper (Th) 2 cells play a key role in the pathogenesis of atopic dermatitis (AD) because of clinical and experimental findings including hyper IgE, eosinophilia and Th2 type cytokine overexpression, etc. In contrast, several observations such as Th1 type cytokine detection in chronic lesions and histological features resembling allergic contact dermatitis suggest that Th1 rather than Th2 cells are important for the pathogenesis of skin lesions. In order to clarify this paradox, we investigated the function of T cell clones established from AD patients. Most T cell clones induced by house dust mite antigen and interleukin (IL)-2 from peripheral blood mononuclear cells of two AD patients exhibited CD4+/ CD8-, CD45RO+/ CD45RA-, and produced high levels of IL-4 and low levels of interferon-gamma (IFN-gamma) after phytohemagglutinin (PHA) (1 microg/ml) stimulation, suggesting a Th2 subtype. When stimulated with a high dose of concanavalin A (conA) (10 microg/ml), however, these clones produced high amounts of IFN-gamma. IL-4 production reached a peak 24 hours after conA (10 ,g/ml) stimulation, whereas IFN-gamma production was increased up to 48 hours after stimulation. The findings of T cell receptor (TCR) stimulation with immobilized anti-CD3 monoclonal antibody (mAb) showed that the suitable strength of TCR stimulation for IFN-y production was higher than for IL-4. Also, in the TCR stimulated condition, the peak of IFN-gamma production was later than that of IL-4. These results indicate that T cell clones which exhibited a Th2 profile under weak stimulation can produce IFN-y in the late phase of stimulation when strong stimuli are used. The results are consistent with the previous observation that IFN-gamma production prominently appears in the chronic and late phase lesions of AD.

Quantification of house dust mite allergens in ambient air.

The house dust mites Dermatophagoides pteronyssinus and Dermatophagoides farinae are important sources of indoor allergens. In sensitized patients, house dust mites induce and exacerbate diseases like asthma bronchiale, rhinitis, and conjunctivitis. The most significant exposure of persons occurs overnight in bed and to a lesser extent, during the daytime while performing activities like vacuum cleaning or bed making. In general, house dust mite antigens are quantified in samples of reservoir dust of carpets or beds. Yet, assessing allergens in ambient air would better represent human exposures because inhalation is the main route of uptake, and a close correlation between levels of floor and air antigens has not yet been proved. Unfortunately, because of extremely low airborne particle concentrations, analyses are difficult to perform and depend on sophisticated sampling strategies, as well as on sensitive immunometric detection assays. Using monoclonal immunoassays, house dust mite antigens, quantified in undisturbed conditions in ambient air, are found at pg/m3 levels. The disturbance of reservoir dust by vacuum cleaning or bed making increases the airborne allergen levels up to ng/m3 concentrations. In this review, we discuss the current knowledge regarding the analysis of airborne house dust mites in both undisturbed and disturbed ambient air. The advantages and disadvantages of different sampling strategies are outlined.

Role of kinins in seasonal allergic rhinitis: Icatibant, a bradykinin B2 receptor antagonist, abolishes the hyperresponsiveness and nasal eosinophilia induced by antigen

Background: Icatibant, a bradykinin B2 receptor antagonist, inhibits the reduction in nasal patency after challenge with house dust mite antigen in sensitive subjects and abolishes the nasal hyperresponsiveness induced by platelet-activating factor in nonatopic subjects. Objective: We sought to investigate the effect of icatibant on the response to nasal antigen challenge in subjects with seasonal allergic rhinitis. Methods: Patients allergic to grass pollen antigen (n = 9-13) were included in a double-blind, randomized-block, placebo-controlled, crossover study outside the pollen season. Subjects first received an intranasal spray of icatibant (200 μg per nostril) or a saline control. Subjects were then challenged with antigen or diluent (control), and their responses were monitored by using acoustic rhinometry. Six hours later, nasal lavage fluid was collected and quantified for inflammatory cells and various inflammatory mediators (kinin, eosinophil cationic protein, IL-5, and IL-8). At 24 hours, the response of the nasal airways to 200 μg of histamine was assessed, and a further nasal lavage was carried out. Results: Antigen challenge caused a significant increase in nasal obstruction and albumin extravasation, which was not affected by icatibant. Nasal hyperresponsiveness to histamine was present 24 hours after antigen and was abolished by pretreatment with icatibant. Icatibant also reduced the antigen-induced increase in eosinophils, eosinophil cationic protein, kinin, and IL-8 in nasal lavage fluid. Conclusion: Pretreatment with icatibant does not affect the acute inflammatory response in seasonal allergic rhinitis. However, our results imply the involvement of kinins and the bradykinin B2 receptor in the development of antigen-induced hyperresponsiveness and the associated eosinophilia in the human nasal airway. (J Allergy Clin Immunol 2001;107:105-13.)

Attenuated Allergic Responses to House Dust Mite Antigen in Feed-Restricted Rats

Caloric restriction has been shown to alter a broad range of immunological end points in both experimental animals and humans. The objective of this study was to investigate the effect of short-term moderate feed restriction (25% reduction) on allergic immune responses in Brown Norway rats. After 3 weeks of acclimation to their feed regimens, rats were sensitized and 2 weeks later challenged with house dust mite (HDM) antigen via intratracheal instillation. Feed restriction resulted in lower levels of antigen-specific IgE in serum and reduced antigen specific lymphoproliferative activity in pulmonary lymph nodes. Feed restriction also attenuated pulmonary inflammation, as evidenced by lower levels of lactate dehydrogenase and total protein, decreased infiltration of neutrophils and eosinophils, and reduced secretion of pro-inflammatory cytokine tumor necrosis factor (TNF)-[alpha] in bronchoalveolar lavage fluid. In addition, feed restriction decreased TNF-[alpha] secretion in serum and decreased mRNA expression of TNF-[alpha] and interleukin-6 in pulmonary lymph nodes. We conclude that feed restriction strongly dampened the allergic immune responses to HDM in rats and that this attenuation was associated with decreased expression and secretion of pro-inflammatory cytokines.

Attenuated allergic responses to house dust mite antigen in feed-restricted rats.

Caloric restriction has been shown to alter a broad range of immunological end points in both experimental animals and humans. The objective of this study was to investigate the effect of short-term moderate feed restriction (25% reduction) on allergic immune responses in Brown Norway rats. After 3 weeks of acclimation to their feed regimens, rats were sensitized and 2 weeks later challenged with house dust mite (HDM) antigen via intratracheal instillation. Feed restriction resulted in lower levels of antigen-specific IgE in serum and reduced antigen specific lymphoproliferative activity in pulmonary lymph nodes. Feed restriction also attenuated pulmonary inflammation, as evidenced by lower levels of lactate dehydrogenase and total protein, decreased infiltration of neutrophils and eosinophils, and reduced secretion of pro-inflammatory cytokine tumor necrosis factor (TNF)-[alpha] in bronchoalveolar lavage fluid. In addition, feed restriction decreased TNF-[alpha] secretion in serum and decreased mRNA expression of TNF-[alpha] and interleukin-6 in pulmonary lymph nodes. We conclude that feed restriction strongly dampened the allergic immune responses to HDM in rats and that this attenuation was associated with decreased expression and secretion of pro-inflammatory cytokines.

Pollution and the immune response: atopic diseases--are we too dirty or too clean?

The effect of pollutants on the immune system has filled tomes and is almost always controversial whether the topic is disinfectants in drinking water or particulates and lung cancer. Even whether outdoor and indoor air quality is improving or declining has been a source of considerable investigation, consultation and often litigation. Few areas, however, yield so much uncertainty and debate as the role of airborne pollutants in atopy. Atopy is defined as an immunoglobulin E- (IgE) mediated allergic response to environmental antigens and can be manifested as rhinitis, asthma or atopic dermatitis. While there is some debate over whether there has been a real increase in atopy over the last decades, it is indisputable that there has been a dramatic change over the last 200 years. While isolated cases of anaphylaxis had been noted before, allergies were unheard of until the early 19th century. Only 54 years after the first description of hay fever in England in 1819, it was considered an epidemic and a clear association with urbanization had been reported.1 What aspect of urbanization is involved has been much debated. There has been much discussion amongst both experimental immunologists and epidemiologists over whether pollutants are responsible for increased allergic sensitization and/or severity.2,3 In the last few years new studies have supported an alternative explanation, namely the decline in infectious diseases in industrialized countries.4,5 Does this ‘hygiene theory’ toll the death knell for the ‘pollution theory’? In this review I will argue that there is a compelling case to be made for both theories and that even this is not the entire picture.

Allergen provocation augments endotoxin-induced nasal inflammation in subjects with atopic asthma

Background: Recent epidemiologic and in vivo studies have suggested that inhaled endotoxin plays an important role in asthma pathogenesis. Objective: The present study examines the effect of nasal allergen provocation on subsequent endotoxin challenge in subjects with atopic asthma. Methods: By using a split-nose randomized crossover design, individual nares of 12 asthmatic subjects underwent challenge and lavage as follows. Immediately after a baseline nasal lavage, one nares received normal saline, and the other received dust mite antigen. Four hours later, both nares were exposed to either saline or endotoxin. Dust mite antigen (Dermatophagoides farinae) and endotoxin (Escherichia coli 026:B6) doses were 100 AU and 1000 ng, respectively. Postchallenge lavages were done at 8 and 24 hours after the initial challenge. The subjects then returned a minimum of 3 weeks later for crossover to the study arm. Nasal lavage fluid was analyzed for total and differential cell counts, IL-8, IL-6, intercellular adhesion molecule 1, GM-CSF, eosinophil cationic protein, myeloperoxidase, and soluble CD14. Results: A significant increase in the total inflammatory cell count was seen at 8 hours for the dust mite/endotoxin exposure compared with the saline/saline and saline/endotoxin exposures. Differential cell counts revealed a similar neutrophilic and eosinophilic inflammation for the dust mite/endotoxin exposure at 8 hours. Conclusions: These data demonstrate an interaction between allergen and endotoxin exposure in asthmatic subjects, suggesting that a prior allergen challenge significantly augments the endotoxin-induced inflammation. Moreover, these data provide further evidence that concomitant exposure to allergen and endotoxin may be an important factor in asthma pathogenesis. (J Allergy Clin Immunol 2000;105:475-81.)