Systemic Allergic Response Research Articles

Manajemen Rhinitis Alergi

Allergic rhinitis (AR) is an atopic disease characterized by symptoms of nasal congestion, clear rhinorrhea, sneezing, postnasal drop, and nasal pruritis. The disease affects one in six people and is associated with significant morbidity, loss of productivity, and health care costs. Historically, AR was considered a disease process in the nasal airways only, although it is not serious, allergic rhinitis should be considered as a quite serious condition because it can affect the sufferer's quality of life due to the severity of the symptoms experienced and can also cause various complications. However, the development of integrated airway theory has classified AR as a component of the systemic allergic response, with other related conditions, such as asthma and atopic dermatitis, having an underlying systemic pathology. Even though it is not serious, allergic rhinitis should be considered as a quite serious condition because it can affect the sufferer's quality of life due to the severity of the symptoms experienced and can also cause various complications. In addition to nasal symptoms, patients with AR may also experience allergic conjunctivitis, non-productive cough, Eustachian tube dysfunction, and chronic sinusitis. Once diagnosed, AR can be treated in a variety of ways, with intranasal glucocorticoids being the first line of therapy.

Scaleable production of highly loaded protein nanoparticles for immune modulation

Immune modulation and desensitization is a growing field of research and clinical investigation that requires precise delivery of antigens to immune system cells. Nanoparticles (NPs) have emerged as excellent candidates for antigen delivery, particularly in immune desensitization applications. NP-encapsulated protein antigens enable the delivery of protein and co-encapsulated adjuvant to antigen-presenting cells without systemic exposure and allergic response. Here, we show a method for producing poly(lactide-co-glycolide) (PLG) NPs in an efficient, high-yield, and large-scale inhomogeneous precipitation process. The process enables the production of compositionally complex PLG NPs containing protein while also incorporating DNA and E. coli phospholipids as integral adjuvants in the NP vehicle. Orally delivered PLG NPs activate the murine immune system, and encapsulated peanut allergen protein elicits approximately 10-fold lower levels of basophil activation than does unencapsulated protein in basophils isolated from peanut-allergic patients. This efficacy and safety evidence makes these PLG NPs excellent candidates for clinical applications.

Effect of Exposure to Particulate Matter on the Ocular Surface in an Experimental Allergic Eye Disease Mouse Model.

In response to the escalating concern over the effect of environmental factors on ocular health, this study aimed to investigate the impact of air pollution-associated particulate matter (PM) on ocular allergy and inflammation. C57BL/6 mice were sensitized with ovalbumin (OVA) topically and aluminum hydroxide via intraperitoneal injection. Two weeks later, the mice were challenged with OVA and exposed to PM. Three groups-naive, OVA, and OVA-sensitized with PM exposure (OVA + PM) groups-were induced to an Allergic Eye disease (AED) model. Parameters including clinical signs, histological changes, inflammatory cell infiltration, serum OVA-specific immunoglobulins E (IgE) levels, mast cells degranulation, cellular apoptosis and T-cell cytokines were studied. The results demonstrate that exposure with PM significantly exacerbates ocular allergy, evidenced by increased eye-lid edema, mast cell degranulation, inflammatory cytokines (IL-4, IL-5 and TNF-α), cell proliferation (Ki67), and serum IgE, polymorphonuclear leukocytes (PMN), and apoptosis and reduced goblet cells. These findings elucidate the detrimental impact of PM exposure on exacerbating the severity of AED. Noticeably, diminished goblet cells highlight disruptions in ocular surface integrity, while increased PMN infiltration with an elevated production of IgE signifies a systemic allergic response with inflammation. In conclusion, this study not only scientifically substantiates the association between air pollution, specifically PM, and ocular health, but also underscores the urgency for further exploration and targeted interventions to mitigate the detrimental effects of environmental pollutants on ocular surfaces.

Manifestation and associated factors of systemic and local allergy among patients with allergic fungal rhinosinusitis: An observational study.

Allergic fungal rhinosinusitis (AFRS) is a subtype of chronic rhinosinusitis, characterized by excessive immune responses to environmental molds or fungi. The diagnosis and classification of AFRS into systemic and local types remain clinically challenging due to overlapping characteristics. This study investigated the prevalence of AFRS, its manifestation and associated factors in systemic and local AFRS. A total of 200 patients diagnosed with fungal rhinosinusitis underwent both skin provocation tests (SPT) and nasal provocation tests (NPT) to confirm AFRS and classify systemic and local types. Patients were considered to have AFRS if either the SPT or NPT was positive. Among these, patients with systemic AFRS were those who had a SPT positive. Local AFRS was when patients had a negative SPT and a positive NPT. Medical history, serum total IgE level, nasal endoscopy examinations, and CT scans were also recorded. Most patients were female (65.8%), with a mean age of 55.6 years (SD = 14.4). Based on the SPT and NPT results, 31% of patients (n = 62) were diagnosed with AFRS. Among these, 54.8% (n = 34) had systemic AFRS, while 45.2% (n = 28) had local AFRS. Patients with AFRS exhibited significantly higher levels of total IgE, eosinophils, and more pronounced signs and symptoms compared to those without AFRS. However, no statistically significant differences were observed between patients with systemic AFRS and those with local AFRS. AFRS was prevalent in our study. Among patients with AFRS, both systemic AFRS and local AFRS were also prevalent. While allergic indicators and clinical presentations can aid in AFRS diagnosis, minimal distinctions were observed between systemic and local AFRS. A comprehensive assessment incorporating both local and systemic allergic responses through provocation tests, such as a combination of skin and nasal tests, is imperative for optimizing AFRS diagnosis and management.

Self-Assembling Allergen Vaccine Platform Raises Therapeutic Allergen-Specific IgG Responses without Induction of Systemic Allergic Responses.

Allergen immunotherapies are often successful at desensitizing allergic patients but can require life-long dosing and suffer from frequent adverse events including instances of systemic anaphylaxis, leading to poor patient compliance and high cost. Allergen vaccines, in turn, can generate more durable immunological allergen desensitization with far fewer doses. However, like immunotherapies, allergen vaccines are often highly reactogenic in allergic patients, hampering their use in therapeutic settings. In this work, we utilize a peptide-based self-assembling nanofiber platform to design allergen vaccines against allergen B-cell epitopes that do not elicit systemic anaphylaxis when administered subcutaneously to allergic mice. We show that, in contrast to protein vaccines, nanofiber vaccines prevent leakage of allergen material into the vascular compartment, a feature that likely underpins their reduced systemic reactogenicity. Further, we show that our allergen vaccine platform elicits therapeutic IgG antibody responses capable of desensitizing allergic mice to allergen-induced Type I hypersensitivity reactions. Finally, we have demonstrated a proof-of-concept for the therapeutic potential of nanofiber-based peanut allergen vaccines directed against peanut allergen-derived epitopes.

Probiotic Bacteria from Human Milk Can Alleviate Oral Bovine Casein Sensitization in Juvenile Wistar Rats.

This study aims to see if probiotic bacteria from human milk could ameliorate oral cow's milk sensitization. The probiotic potential of the SL42 strain isolated from the milk of a healthy young mother was first determined. Rats were then randomly gavaged with cow's milk casein without an adjuvant or assigned to the control group. Each group was further subdivided into three groups, with each receiving only Limosilactobacillus reuteri DSM 17938, SL42, or a phosphate-buffered saline solution. Body weight, temperature, eosinophils, serum milk casein-specific IgE (CAS-IgE), histamine, and serum S100A8/A9 and inflammatory cytokine concentrations were measured. The animals were sacrificed after 59 days; histological sections were prepared, and the spleen or thymus weights, as well as the diversity of the gut microbiota, were measured. On days 1 and 59, SL42 abridged systemic allergic responses to casein by dropping histamine levels (25.7%), CAS-specific IgE levels (53.6%), eosinophil numbers (17%), S100A8/9 (18.7%), and cytokine concentrations (25.4-48.5%). Analyses of histological sections of the jejunum confirmed the protective effect of probiotic bacteria in the CAS-challenged groups. Lactic acid bacteria and Clostridia species were also increased in all probiotic-treated groups. These findings suggest that probiotics derived from human milk could be used to alleviate cow's milk casein allergy.

Immunotherapy-induced neutralizing antibodies disrupt allergen binding and sustain allergen tolerance in peanut allergy.

In IgE-mediated food allergies, exposure to the allergen activates systemic allergic responses. Oral immunotherapy (OIT) treats food allergies through incremental increases in oral allergen exposure. However, OIT only induces sustained clinical tolerance and decreased basophil sensitivity in a subset of individuals despite increases in circulating allergen-specific IgG in all treated individuals. Therefore, we examined the allergen-specific antibodies from 2 OIT cohorts of patients with sustained and transient responses. Here, we compared antibodies from individuals with sustained or transient responses and discovered specific tolerance-associated conformational epitopes of the immunodominant allergen Ara h 2 recognized by neutralizing antibodies. First, we identified what we believe to be previously unknown conformational, intrahelical epitopes using x-ray crystallography with recombinant antibodies. We then identified epitopes only recognized in sustained tolerance. Finally, antibodies recognizing tolerance-associated epitopes effectively neutralized allergen to suppress IgE-mediated effector cell activation. Our results demonstrate the molecular basis of antibody-mediated protection in IgE-mediated food allergy, by defining how these antibodies disrupt IgE-allergen interactions to prevent allergic reactions. Our approach to studying the structural and functional basis for neutralizing antibodies demonstrates the clinical relevance of specific antibody clones in antibody-mediated tolerance. We anticipate that our findings will form the foundation for treatments of peanut allergy using neutralizing antibodies and hypoallergens.

Effects of coffee intake on airway hypersensitivity and immunomodulation: an in vivo murine study.

Coffee is a complex chemical mixture, with caffeine being the most well-known bioactive substance. The immunomodulatory and anti-inflammatory properties of coffee and caffeine impact health in various aspects, including the respiratory system. The objective is to investigate the effects of coffee and caffeine on airway hyperresponsiveness and allergic reactions, as well as to analyze and compare associated cytokine profiles. BALB/c mice were intraperitoneally sensitized with ovalbumin (OVA) and given OVA inhalation to induce airway hypersensitivity. Two weeks after sensitization, they were intragastrically gavaged with coffee or caffeine, both containing 0.3125 mg caffeine, daily for 4 weeks. Control mice were fed with double-distilled water. Serum OVA-specific antibody levels were measured beforehand and 5 weeks after the first gavage. Airway hyperresponsiveness was detected by whole body plethysmography after gavage. Cytokine levels of bronchoalveolar lavage and cultured splenocytes were analyzed. Coffee effectively suppressed T helper 2-mediated specific antibody response. Airway responsiveness was reduced in mice treated with either coffee or caffeine. Compared to the control, coffee significantly reduced OVA-specific immunoglobulin (Ig) G, IgG1 and IgE antibody responses (P < 0.05). Caffeine also attenuated specific IgG and IgG1 levels, though IgE level was unaffected. Coffee significantly reduced interleukin (IL)-4 and increased IL-10 concentration in spleen cells and bronchoalveolar lavage fluid (P < 0.05). Coffee effectively attenuated airway hyperresponsiveness and systemic allergic responses induced by OVA food allergen in mice. As a complex composition of bioactive substances, coffee displayed enhanced immunomodulatory and anti-inflammatory effects than caffeine.

Allergic Response

The term hypersensitivity refers to diseases caused by an immune response, regardless of whether the response is against a pathogen, nonpathogen, or self and regardless of whether the response is directed by antibodies, lymphocytes, or innate pathways. The term anaphylaxis was coined in 1902 by Charles Richet, who received the Nobel Prize in 1913; this systemic allergic response is now known to be an immediate hypersensitivity reaction, initiated by allergen delivered to a host having allergen-specific IgE, thereby causing an IgE-mediated immunologic response and activating mast cells and basophils to secrete bioactive mediators. In 2005, the National Institutes of Health organized a consensus conference to develop a working definition of anaphylaxis, designed to be used by physicians at the bedside, as a serious allergic reaction that is rapid in onset, typically eliciting various combinations of cutaneous, cardiovascular, respiratory, and gastrointestinal manifestations, and may cause death.1,2 This facilitated the early treatment of such patients with epinephrine. Confusion arises over the misapplication of the term allergy or hypersensitivity to describe any untoward reaction to food, medications, or environmental exposures. Furthermore, non–IgE-mediated forms of local and systemic mast cell or basophil activation events can occur, causing signs and symptoms similar to those mediated by IgE. This review contains 3 figures, 9 tables, and 62 references. Keywords: allergy, hypersensitivity, anaphylaxis, interleukin, chemokines, immunoglobulin E, mast cell, eosinophil

Granzyme B Contributes to Barrier Dysfunction in Oxazolone-Induced Skin Inflammation through E-Cadherin and FLG Cleavage

Atopic dermatitis (AD) is the most common inflammatory skin condition. Skin barrier dysfunction is of major importance in AD because it facilitates allergen sensitization and systemic allergic responses. Long regarded as a pro-apoptotic protease, emerging studies indicate granzyme B (GzmB) to have extracellular roles involving the proteolytic cleavage of extracellular matrix, cell adhesion proteins, and basement membrane proteins. Minimally expressed in normal skin, GzmB is elevated in AD and is positively correlated with disease severity and pruritus. We hypothesized that GzmB contributes to AD through extracellular protein cleavage. A causative role for GzmB was assessed in an oxazolone-induced murine model of dermatitis, comparing GzmB-/- mice with wild-type mice, showing significant reductions in inflammation, epidermal thickness, and lesion formation in GzmB-/- mice. Topical administration of a small-molecule GzmB inhibitor reduced disease severity compared with vehicle-treated controls. Mechanistically, GzmB impaired epithelial barrier function through E-cadherin and FLG cleavage. GzmB proteolytic activity contributes to impaired epidermal barrier function and represents a valid therapeutic target for AD.

Defining biomarkers to predict symptoms in subjects with and without allergy under natural pollen exposure

Pollen exposure induces local and systemic allergic immune responses in sensitized individuals, but nonsensitized individuals also are exposed to pollen. The kinetics of symptom expression under natural pollen exposure have never been systematically studied, especially in subjects without allergy. We monitored the humoral immune response undernatural pollen exposure to potentially uncover nasal biomarkers for in-season symptom severity and identify protective factors. We compared humoral immune response kinetics in a panel study of subjects with seasonal allergic rhinitis (SAR) and subjects without allergy and tested for cross-sectional and interseasonal differences in levels of serum and nasal, total, and Betula verrucosa 1-specific immunoglobulin isotypes; immunoglobulin free light chains; cytokines; and chemokines. Nonsupervised principal component analysis was performed for all nasal immune variables, and single immune variables were correlated with in-season symptom severity by Spearman test. Symptoms followed airborne pollen concentrations in subjects with SAR, with a time lag between 0 and 13 days depending on the pollen type. Of the 7 subjects with nonallergy, 4 also exhibited in-season symptoms whereas 3 did not. Cumulative symptoms in those without allergy were lower than in those with SAR but followed the pollen exposure with similar kinetics. Nasal eotaxin-2, CCL22/MDC, and monocyte chemoattactant protein-1 (MCP-1) levels were higher in subjects with SAR, whereas IL-8 levels were higher in subjects without allergy. Principal component analysis and Spearman correlations identified nasal levels of IL-8, IL-33, and Betula verrucosa 1-specific IgG4 (sIgG4) and Betula verrucosa 1-specific IgE (sIgE) antibodies as predictive for seasonal symptom severity. Nasal pollen-specific IgA and IgG isotypes are potentially protective within the humoral compartment. Nasal levels of IL-8, IL-33, sIgG4 and sIgE could be predictive biomarkers for pollen-specific symptom expression, irrespective of atopy.

Epicutaneous Exposure to Peanut Oil Induces Systemic and Pulmonary Allergic Reaction in Mice

Background: The prevalence of peanut allergy (PA) is constantly on the rise. Atopic dermatitis (AD) is a major risk factor for developing food allergy. Some bath oils and skin creams used for treating AD contain peanut oil, and it has been suggested that exposure to peanut allergens through a disrupted skin barrier is a potential cause of PA. Our aim was to investigate whether application of peanut oil to irritated skin causes a systemic or respiratory allergic response to peanuts in an animal model. Methods: BALB/c mice underwent epicutaneous sensitization with either peanut oil (PM, n = 9) or phosphate buffered solution (controls, n = 9) daily for 5 consecutive days. Ten days after the last exposure the mice were challenged with intranasal peanut protein for 5 consecutive days. Bronchial alveolar lavage fluid was collected for cellular studies and measurement of cytokine levels. Sera were collected for immunoglobulin E (IgE) measurement. Results: Epicutaneous peanut oil sensitization increased leukocyte and eosinophil counts and interleukin-13 levels (p = 0.003, p = 0.0006 and p = 0.03, respectively), in addition to increasing total serum IgE (p = 0.03). Conclusions: The results suggest that topical application of peanut oil may play a role in the etiology of PA.

Perinatal antibiotic exposure alters composition of murine gut microbiota and may influence later responses to peanut antigen

BackgroundAccumulating evidence suggests that the gut microbiota shapes developmental processes within the immune system. Early life antibiotic use is one factor which may contribute to immune dysfunction and the recent surge in allergies by virtue of its effects on gut microbiota.Objective and methodsAs a first step towards determining whether a relationship exists between perinatal antibiotic induced changes in the gut microbiota and the later development of a peanut allergy, we exposed newborn mice to either the broad-spectrum antibiotic vancomycin or to a vehicle for 6 weeks and then used a novel murine model of peanut allergy.ResultsEarly-life treatment with vancomycin resulted in a significant shift in the gut microbiota community characterized by a reduction in the abundance of firmicutes and preponderance of inflammatory proteobacteria. Mice with an antibiotic-altered microbiota, showed a localized allergic-like response characterized by ear swelling and scratching following intra-dermal peanut antigen challenge. Likewise, circulating IgE levels were increased in antibiotic-treated mice, but no evidence of a systemic allergic or anaphylactic-like response was observed. Importantly, we utilized the naturally occurring pro-inflammatory cytokine, tumor necrosis factor-α (TNF-α), rather than the more commonly used cholera toxin, as an adjuvant together with the peanut antigen.ConclusionOur data suggest that early antibiotic exposure promotes a shift in the gut microbiota community that may in turn, influence how mice later respond to a TNF-α + antigen challenge. However, further studies verifying the capacity of microbiota restoration to protect against allergic responses will be needed to confirm a causal role of antibiotic-induced microbiota variations in promoting allergic disease phenotypes.

Galectin-1 inhibits oral-intestinal allergy syndrome.

Background and aimsThe pathogenesis of oral-intestinal allergy syndrome (OIAS) has not been well understood. Published data indicate that galectin (Gal) 1 has immune regulatory functions. This study tests a hypothesis that Gal1 inhibits oral-intestinal allergy syndrome.MethodsMice were sensitized to peanut extracts (PE) via the buccal mucosa with or without using Gal1 together.ResultsUpon re-exposure to specific antigen, the OIAS mice showed the systemic allergic response, the oral allergic reactions, and intestinal allergic inflammation, including increases in serum histamine, drop of the core temperature, higher levels of PE-specific IgE and interleukin (IL)-4. Increases in mast cell and eosinophil in the oral mucosa and intestinal mucosa were also observed. The OIAS was inhibited by co-administration with Gal1 via a mechanism of suppressing micro RNA (miR)-98 and reversing the expression of IL-10 in CD14+ cells in the intestine.ConclusionsThe OIAS can be induced by applying specific antigens to the oral mucosa, which can be inhibited by co-administration with Gal1.

Food Allergy: Our Evolving Understanding of Its Pathogenesis, Prevention, and Treatment.

Food allergy is defined as an IgE-mediated hypersensitivity response to ingested food with allergic symptoms ranging from urticaria to life-threatening anaphylaxis. Food allergy is thought to develop because of (1) failed induction of tolerance upon initial exposure to food antigen or (2) breakdown of established tolerance to food antigen. We review current understanding of the pathogenesis, epidemiology, and natural history of food allergy, including the unconventional IgE-mediated food allergy to mammalian meat known as alpha-gal food allergy. We highlight emerging data on food allergy treatment and prevention, emphasizing the growing appeal of manipulating the gut microenvironment using probiotics and helminth products to blunt systemic allergic responses to food.

An Adjuvant-Free Mouse Model of Transdermal Sensitization and Oral Elicitation of Anaphylaxis to Shellfish

Background: Shellfish (SF) allergy is a leading cause of systemic anaphylaxis in humans. An adjuvant-free mouse model to evaluate allergenicity and oral anaphylaxis to SF is currently unavailable. Here, we tested the hypothesis that transdermal exposure (TDE) to SF protein extract (SFPE) not only elicits a systemic allergic immune response but also will clinically sensitize mice for oral anaphylaxis. Methods: Adult BALB/c female mice (6-8 weeks of age) were exposed to saline or SFPE once a week for 4 weeks using a transdermal sensitization method. Systemic SF-specific IgE, IgG1 and IgG2a and total (t)IgE responses were measured using ELISA. Systemic anaphylaxis upon oral SFPE administration was assessed according to clinical symptoms and the hypothermia shock response (HSR). Using individual mouse data, the correlation between the readouts of allergenicity was determined using Pearson's analysis. Spleen-cell IL-4 and IFN-γ responses were determined using primary cell culture and ELISA. Results: TDE to SFPE resulted in marked systemic specific (s)IgE, tIgE, IgG1 and IgG2a responses. Oral challenge with SFPE in sensitized mice (but not controls) elicited systemic anaphylactic clinical reactions and HSR. A strong correlation was observed between sIgE, tIgE and HSR. Spleen cells isolated from allergic mice (but not controls) exhibited memory IL-4 and IFN-γ cytokine responses. Conclusion: We report a novel adjuvant-free mouse model of SF allergy with robust quantifiable and correlated readouts of allergenicity that may be used in basic biomedical, preclinical and applied food/nutrition research on SF allergy.

Maternal exposure to GOS/inulin mixture prevents food allergies and promotes tolerance in offspring in mice.

Food allergies affect 4-8% of children and are constantly on the rise, thus making allergies a timely issue. Most importantly, prevention strategies are nonexistent, and current therapeutic strategies have limited efficacy and need to be improved. One alternative to prevent or reduce allergies, particularly during infancy, could consist of modulating maternal immunity and microbiota using nondigestible food ingredients, such as prebiotics. For this purpose, we studied the preventive effects of prebiotics in Balb/c mothers during pregnancy and breastfeeding on food allergy development in offspring mice. After weaning, the offspring from mothers that were exposed to GOS/inulin mixture or fed a control diet were intraperitoneally sensitized to wheat proteins to induce a systemic allergic response and orally exposed to the same allergen. Immunological, physiological, and microbial parameters were analyzed. GOS/inulin mixture diet modified the microbiota of mothers and their offspring. Offspring from mothers that received GOS/inulin prebiotics were protected against food allergies and displayed lower clinical scores, specifically of IgE and histamine levels, compared to offspring from mothers fed a control diet. Moreover, GOS/inulin supplementation for the mother resulted in stronger intestinal permeability in the offspring. Enhancement of the regulatory response to allergic inflammation and changes in the Th2/Th1 balance toward a dampened Th2 response were observed in mice from GOS/inulin mixture-exposed mothers. The treatment of pregnant and lactating mice with nondigestible GOS/inulin prebiotics promotes a long-term protective effect against food allergies in the offspring.

Toxoplasma gondii infection modulate systemic allergic immune response in BALB/c mice

The increased prevalence of allergies in developed countries has been attributed to a reduced exposure to some microbes. In agreement with epidemiological studies, we previously showed that Toxoplasma gondii infection prevents allergic airway inflammation. The mechanisms would be related to the strong Th1 response induced by the parasite and to regulatory cell induction. Herein we further characterized whether T. gondii allergy modulation extents to a systemic level or if it is limited to the lung. Parasite infection before allergic sensitization resulted in a diminished Th2 cytokine response and, when sensitized during acute infection, an increased in TGF-β production was detected. Allergen specific T cell proliferation was also reduced. Sensitization during both acute and chronic phases of infection resulted in a decreased anaphylaxis reaction. Our results extend earlier work and show that, in addition to lung airway inflammation, T. gondii infection can suppress allergic responses at systemic level. These results open the possibility that this protozoan infection could modulate other allergic disorders such as atopic dermatitis or oral allergies. Understanding the mechanisms by which different microorganisms regulate inflammation may potentially lead to the development of strategies aimed to control atopic diseases.

An intratracheal challenge murine model of asthma: can bronchial inflammation affect the nose?

PurposeExtensive data support the influence of the upper airway on lower airway inflammation and pathophysiology in allergic disease. However, few studies have focused on allergic inflammation in the nose after an isolated lower airway allergen challenge, a situation that can exist clinically when human subjects breathe primarily through the mouth, as occurs when nasally congested. This study used a mouse model to investigate whether upper airway inflammation and hyperresponsiveness were induced by an isolated lower airway allergen challenge.MethodsBALB/c mice were sensitized by systemic intraperitoneal injection of ovalbumin/saline and challenged with intratracheal ovalbumin/saline. Inflammation in the nose and lungs was assessed by cytology and histology of nasal tissues and bronchoalveolar lavage fluid (BALF), while nasal airway resistance and response were measured over 3 days post-challenge.ResultsIntratracheal application of an allergen in anaesthetized mice resulted in exclusive deposition in the lower airway. Compared to control animals, ovalbumin-sensitized mice after challenge showed bronchial hyperreactivity and increased IL-5 in the serum BALF, as well as eosinophil infiltration in the lungs. However, nasal histology of the ovalbumin-sensitized mice showed no increase in eosinophil infiltration. The nasal lavage fluid revealed no increase in eosinophils or IL-5, and the nasal airway resistance did not increase after challenge either.ConclusionsIn a mouse allergy model, exclusive allergen challenge of the lower airway can elicit a pulmonary and systemic allergic response, but does not induce upper airway inflammatory or physiological responses.

Influenza A infection enhances antigen-induced airway inflammation and hyperresponsiveness in young but not aged mice.

Although morbidity and mortality rates from asthma are highest in patients > 65 years of age, the effect of older age on airway inflammation in asthma is not well established. To investigate age-related differences in the promotion of allergic inflammation after influenza A viral respiratory infection on antigen-specific IgE production, antigen-induced airway inflammation and airway hyperresponsiveness in mice. To accomplish this objective, the following model system was used. Young (6 week) and aged (18 months) BALB/c mice were first infected with a non-lethal dose of influenza virus A (H/HKx31). Mice were then ovalbumin (OVA)-sensitized during the acute infection (3-days post inoculation) and then chronically underwent challenge to the airways with OVA. Forty-eight hours after the final OVA challenge, airway hyperresponsiveness (AHR), bronchoalveolar fluid (BALF) cellular and cytokine profile, antigen-specific IgE and IgG1, and lung tissue inflammation were measured. Age-specific differences were noted on the effect of a viral infection, allergic sensitization, airway inflammation and airway hyperresponsiveness. Serum OVA-specific IgE was significantly increased in only the aged mice infected with influenza virus. Despite greater morbidity (e.g. weight loss and sickness scores) during the acute infection in the 18-month old mice that were OVA-sensitized, there was little effect on the AHR and BALF cellular differential. In contrast, BALF neutrophils and AHR increased, but eosinophils decreased in 6-week mice that were OVA-sensitized during an acute influenza infection. With increased age in a mouse model, viral infection prior to antigen sensitization affects the airway and systemic allergic response differently. These differences may reflect distinct phenotypic features of allergic inflammation in older patients with asthma.