Airway Inflammation In Murine Model Research Articles

Purified aged garlic extract modulates allergic airway inflammation in BALB/c mice.

Garlic is known as a potent spice and a medicinal herb with broad therapeutic properties ranging from antibacterial to anticancer and anticoagulant. Our previous studies have shown some immunoregulatory effects for aged garlic extract, suggesting a key role for 14-kD glycoprotein of garlic in shifting the cytokine pattern to T helper-1. In present study, we investigated the effect of 1, 2, and 3 times intraperitoneal injections of aged garlic extract on an established allergic airway inflammation in murine model (BALB/c mice). The garlic extract, isolated by biochemical method, includes proteins precipitation by ammonium sulfate. After injection of the aged garlic extract, IFN-, anti allergen specific IgE and IgG1 were measured in lavage and serum by ELISA and histological assessment was performed on the lung tissues. The results indicated that three-time intra peritoneal injections of the aged garlic extract caused a significant decrease in the hallmark criteria of allergic airway inflammation levels which included eosinophil percentage in lavage, peribronchial lung eosinophils, IgG1 level in lavage and serum, mucous producing goblet cells grade and peribronchial and perivascular inflammation. Our findings in the present research suggested that aged garlic extract has the potential of attenuation of inflammatory features of allergic airway inflammation in murine model.

Differential suppression of allergen‐induced airway inflammation in murine model of asthma by lactic acid bacteria

Differential suppression of allergen‐induced airway inflammation in murine model of asthma by lactic acid bacteria

Severity of murine arthritis induced by Freund's complete adjuvant is reduced by prior infection with the tapeworm parasite Hymenolepis diminuta

Infection with helminth parasites can prevent or reduce the severity of colitis and airway inflammation in murine models of human inflammatory bowel disease and asthma. We postulated that infection with H. diminuta, which is spontaneously expelled from mice, would ameliorate the inflammation evoked by direct injection of Freund's complete adjuvant (FCA) into the knee joint, as a model of inflammatory joint disease. Male mice were orally gavaged with 5 viable H. diminuta cysticercoids in 100μl PBS and 8 days later received FCA (50 μl) into the right knee joint. Controls: a) PBS gavage + PBS knee injection, b) H. diminuta gavage + PBS injection, c) PBS gavage + FCA injection. Knee diameter was measured over a 7 day period and on sacrifice, blood samples were collected, spleen cells stimulated for cytokine production, knee joints extracted for myeloperoxidase (MPO) activity and RT‐PCR performed for cytokine mRNA expression. Mice infected with H. diminuta were significantly protected from FCA‐induced arthritis as shown by reduced knee swelling, fewer circulating neutrophils, lower MPO levels in the joint and reduced splenocyte TNFα production. Thus, our results show that prior infection with the helminth parasite, H. diminuta, significantly protects mice from the arthritic effects of FCA. Funded by CIHR.

EBI3 Deficient Cells Can Produce Comparable Levels of INF-g in the Presence of IL12

Previously we have shown that EBI3 deficient CD+T cells compared to wild type mice displayed defective IFN-g production and reduced Th1 mediated airway inflammation by using murine model of airway inflammation. Based on these findings, we examined the T cell responses in vitro to determine if EBI3 deficiency had an effect on IFN-g production.

Mutated Glutathione-S-Transferase Reduced Airway Inflammation In Murine Model

Oxidative stress contributes in the pathogenesis of asthma. Glutathione-s-transferase (GST) is an antioxidant and its deficiency increases the risk of developing asthma. The present study investigates the effect of GST and mutated GST (mGST) with reduced IgE binding in murine model of airway inflammation.

Five‐aminoimidazole‐4‐carboxamide‐1‐β‐4‐ribofuranoside attenuates poly (I:C)‐induced airway inflammation in a murine model of asthma

Asthma can frequently be induced or exacerbated by respiratory viral infections. Oxidative stress might also play an essential role in the pathogenesis of allergic airway diseases, indicating that antioxidant therapy may have a potential effect in controlling allergic airway diseases. Recent studies showed that 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) has the potential ability to modulate NADPH oxidase activity, indicating the antioxidant activity of AICAR. This study investigated the inhibitory effects of AICAR as an anti-inflammatory modulator on allergic airway inflammation in murine animal models. The anti-inflammatory effects of AICAR were evaluated in two experimental asthma models: (1) an ovalbumin (OVA)-induced experimental asthma model and (2) an OVA plus polyinosinic-polycytidylic acid [poly (I:C)]-induced experimental asthma model to mimic respiratory viral infections. The inhibitory effects of AICAR in poly (I:C)-mediated signalling for NF-kappaB activation and production of TNF-alpha were analysed in vitro. AICAR was shown to have a marginal inhibitory effect in an OVA-induced asthma model. Interestingly, AICAR significantly attenuated poly (I:C)-induced airway hyperresponsiveness and airway inflammation, as shown by the attenuation of the influx of total inflammatory cells and soluble products into bronchoalveolar lavage fluid, such as macrophages, eosinophils, IL-5, IL-13, TNF-alpha and IFN-gamma. AICAR also significantly reduced the serum levels of OVA-specific IgE and IgG2a antibodies. Histologic and flow cytometric studies showed that AICAR inhibited poly (I:C)-induced lung inflammation and the infiltration of CD11b+CD11c+ dendritic cells into the lung. Moreover, AICAR effectively inhibited poly (I:C)-mediated activation of NF-kappaB and the production of TNF-alpha. These findings suggest that AICAR may be a novel immunomodulator with promising beneficial effects for the treatment of respiratory viral infection in airway allergic diseases.

Interference of methysergide, a specific 5‐hydroxytryptamine receptor antagonist, with airway chronic allergic inflammation and remodelling in a murine model of asthma

Airway remodelling encompasses the structural changes observed in asthmatic airways. Mast cells, through the release of histamine and 5-hydroxytryptamine (serotonin), are implicated in early asthmatic reactions, bronchoconstriction and mucosal oedema, and in the development of bronchial hyperresponsiveness. However, the association between serotonin and remodelling processes in murine model of airways inflammation remains to be elucidated. As serotonin is released by murine mast cells upon antigen challenge, we tested the hypothesis of its involvement in the development of inflammatory and remodelling processes in a murine model of chronic airway inflammation following prolonged allergen challenge. Methods BALB/c mice were exposed to aerosolized ovalbumin for 20 min 2 days a week, for 4 consecutive weeks. Two hours before each challenge, they were treated with methysergide (intranasally, 40 microg/kg). Forty-eight hours after the last aerosol challenge, bronchoalveolar lavage (BAL) and lung tissue were collected for analysis. Methysergide inhibited the allergen-induced increase in airway eosinophilia, reduced T helper type 2 (Th2) cytokines in lung, spleen or thoracic lymph nodes, and specific IgE levels. The extravasation of plasma and fibronectin production in the lung, and collagen deposition in the lung were also inhibited after methysergide treatment. Although methysergide treatment induced an increase in IFN-gamma levels, experiments with neutralizing antibody suggest that this is not responsible for inhibition. In addition, instillation of serotonin to immunized mice induced eosinophil recruitment to BAL, Th2 cytokine production and fibronectin release in lung as well as collagen deposition. Serotonin may contribute to the development and maintenance of remodelling through the release of cytokines and of fibrogenic mediators. Serotonin should therefore be considered as relevant for the development and maintenance of airway remodelling.

T-Cell Receptor (TCR)-Mediated Upregulation of BLT1 (LTB4 Receptor) Expression and Activation of Human T Cells by LTB4

RATIONALE: BLT1, the high affinity receptor for leukotriene B4 (LTB4), has been implicated in the development of airway hyperresponsiveness and allergic airway inflammation in murine models and in asthma (JACI 117:577-582, 2006). This study investigated the induction of BLT1 expression and activation of human peripheral blood T cells via LTB4-BLT interactions. METHODS: T cells were isolated to high purity (>97% CD3+) by negative selection from peripheral blood of healthy human subjects. Cells were stimulated in culture with anti-CD3/anti-CD28, followed by analysis of BLT1 expression on CD4+ or CD8+ T cells. Activation of T cells following ligation of BLT1 by LTB4 was assessed by intracellular Ca2+ mobilization and mitogen-activated protein kinase (MAPK) phsophorylation. RESULTS: BLT1 expression was not detected on freshly isolated, resting (non-stimulated) CD4 or CD8 T cells. Following activation of cells with anti-CD3/anti-CD28, BLT1 expression was induced in a time-dependent fashion on both CD4 and CD8 T cells. Addition of LTB4 triggered intracellular Ca2+ mobilization and MAPK phosphorylation in activated but not in resting CD4 and CD8 T cells. CONCLUSIONS: Both CD4 and CD8 T cells express BLT1 upon TCR activation. Engagement of BLT1 with LTB4 results in activation of these cells. Together, with observations made in mice, these findings suggest an important role for the LTB4-BLT1.

Effects of overexpression of IL-10, IL-12, TGF-β and IL-4 on allergen induced change in bronchial responsiveness

BackgroundAn increasing prevalence of allergic diseases, such as atopic dermatitis, allergic rhinitis and bronchial asthma, has been noted worldwide. Allergic asthma strongly correlates with airway inflammation caused by the unregulated production of cytokines secreted by allergen-specific type-2 T helper (Th2) cells. This study aims to explore the therapeutic effect of the airway gene transfer of IL-12, IL-10 and TGF-β on airway inflammation in a mouse model of allergic asthma.MethodsBALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injections with OVA and challenged by nebulized OVA. Different cytokine gene plasmids or non-coding vector plasmids were instilled daily into the trachea up to one day before the inhalatory OVA challenge phase.ResultsIntratracheal administration of IL-10, IL-12 or TGF-β can efficiently inhibit antigen-induced airway hyper-responsiveness and is able to largely significantly lower the number of eosinophils and neutrophils in bronchoalveolar lavage fluid of ovalbumin (OVA) sensitized and challenged mice during the effector phase. Furthermore, the effect of IL-10 plasmids is more remarkable than any other cytokine gene plasmid. On the other hand, local administration of IL-4 gene plasmids before antigen challenge can induce severe airway hyper-responsiveness (AHR) and airway eosinophilia.ConclusionOur data demonstrated that anti- inflammatory cytokines, particularly IL-10, have the therapeutic potential for the alleviation of airway inflammation in murine model of asthma.

Polyethylenimine‐based antisense oligodeoxynucleotides of IL‐4 suppress the production of IL‐4 in a murine model of airway inflammation

Interleukin-4 (IL-4) plays a crucial role as an inflammatory mediator in allergic asthma via inducing Th2 inflammation and IgE synthesis. To develop an effective therapeutic agent which specifically inhibits production of IL-4, antisense oligodeoxynucleotides (AS-ODNs) against murine IL-4 mRNA were generated and complexed with polyethylenimine (PEI) to improve intracellular delivery. AS-ODNs were generated against the translation initiation region of murine IL-4 mRNA, and complexed with linear PEI. In vitro efficacy of AS-ODNs/PEI complexes was tested by measuring IL-4 production in the D10.G4.1 cell line, and cytotoxicity was tested by XTT assay. Physicochemical properties of polyplexes were examined using atomic force microscopy (AFM) and DNase I protection assay. In vivo effects of IL-4 AS-ODNs/PEI complexes were tested in a murine model of airway inflammation. IL-4 concentrations in the bronchoalveolar lavage (BAL) fluid and circulating IgE levels were measured by ELISA, and histological analysis of lung tissues was performed. IL-4 AS-ODNs/PEI complexes were spheres with an average diameter of 98 nm and resistant to DNase I-mediated degradation. IL-4 AS-ODNs/PEI complexes showed up to 35% inhibition of IL-4 production in D10.G4.1 cells without causing any toxicity, while naked ODNs gave less than 1% reduction. Furthermore, IL-4 AS-ODNs/PEI complexes were effective in suppressing secretion of IL-4 (up to 30% reduction) in the BAL fluid in an ovalbumin-sensitized murine model of airway inflammation. Circulating IgE levels were decreased, and airway inflammation was alleviated by treatment with IL-4 AS-ODNs polyplexes. These data demonstrate that complexation of IL-4 AS-ODNs with PEI provides a potential therapeutic tool in controlling inflammation associated with allergic asthma, and further presents an opportunity to the development of clinical therapy based on combination of multiple AS-ODNs of cytokines and/or signaling effectors involved in Th2 inflammation and eosinophilia.

An antigen-independent but not antigen-specific TH1 response provides protection in the murine airway inflammation model

Atopic disorders are associated with an imbalanced T(H) cell response biased toward a strong T(H)2 type, resulting in excessive production of IgE antibodies, eosinophil recruitment and activation, and mast cell degranulation. Restoring the T(H)1-T(H)2 balance by increasing the antigen-specific T(H)1 response has been pursued for specific allergy immunotherapy. Synthetic oligodeoxynucleotides containing unmethylated CG dinucleotides (CpG) are strong T(H)1 adjuvants and are being investigated for allergy immunotherapy. This study was designed to investigate the protective role of antigen-specific T(H)1 responses induced by epidermal powder immunization with ovalbumin (OVA) and CpG in a murine airway inflammation model. An allergy model was used in which BALB/c mice were sensitized and then challenged with OVA. Mice received prophylactic or therapeutic immunizations with OVA, CpG, or both. After challenge, pulmonary inflammation and cell infiltration were measured on the basis of BAL cell counts and lung histology. Immune response was determined by measuring the levels of lavage cytokines and serum antibodies. Coadministration of OVA and CpG by means of subcutaneous injection or epidermal powder immunization, although inducing a strong T(H)1 response, neither suppressed T(H)2 cytokines nor offered protection against pulmonary eosinophilia and histopathology in a mouse challenge model. However, when CpG was used as a stand-alone treatment of previously sensitized animals, protection against allergic airway inflammation was observed. After challenge with OVA, eosinophilia was suppressed in the lungs of the CpG-treated mice. This finding argues against the approach of boosting an allergen-dependent T(H)1 response and favors induction of an antigen-independent T(H)1 response for allergy immunotherapy.

Identified a morpholinyl-4-piperidinylacetic acid derivative as a potent oral active VLA-4 antagonist

An investigation into the structure–activity relationship of a lead compound, prolyl-5-aminopentanoic acid 4, led to the identification of a novel series of 4-piperidinylacetic acid, 1-piperazinylacetic acid, and 4-aminobenzoic acid derivatives as potent VLA-4 antagonists with low nanomolar IC 50 values. A representative compound morpholinyl-4-piperidinylacetic acid derivative ( 13d: IC 50 = 4.4 nM) showed efficacy in the Ascaris-antigen sensitized murine airway inflammation model by oral administration.

Complex role of the IL-4 receptor alpha in a murine model of airway inflammation: expression of the IL-4 receptor alpha on nonlymphoid cells of bone marrow origin contributes to severity of inflammation.

Recent studies have suggested the IL-4Ralpha expressed on lung epithelium is necessary for TH2-mediated goblet cell differentiation and mucus hypersecretion in a murine model of allergic lung disease. However, the IL-4Ralpha is expressed on numerous cell types that could contribute to the overall pathology and severity of asthma. The relative role of the receptor on these cells has not yet been conclusively delineated. To dissect the contribution of IL-4Ralpha in the development of pulmonary allergic responses, we generated murine radiation bone marrow (BM) chimeras. BM from IL-4Ralpha(+) or IL-4Ralpha(-) mice was transferred into recipient mice that expressed or lacked IL-4Ralpha. In the absence of IL-4Ralpha in recipient mice, there was no goblet cell metaplasia or mucus hypersecretion in response to OVA, even in the presence of TH2 cells and substantial eosinophilic infiltration. More importantly, we found that expression of the IL-4Ralpha on a nonlymphoid, MHC class II(+), BM-derived cell type contributes to the severity of inflammation and mucus production. These results suggest that IL-4 and IL-13 contribute to the development of allergic inflammation by stimulating a complex interaction between IL-4Ralpha(+) cell types of both bone marrow and non-bone marrow origin.

Induction of oral tolerance by CpG-ODNs in a murine model of asthma

Rationale Oligodeoxynucleotides containing CpG motifs (CpG-ODNs), administered systemically or into the airway, protect against eosinophilic airway inflammation in murine models of asthma; in this study, we evaluated the effects of oral administration of CpG-ODNs on atopic responses. Methods CpG-ODNs (10–1,000 μg) were administered by gastric gavage to mice at various time-points relative to sensitization to and challenge with the experimental allergen, ovalbumin (OVA); to evaluate the effect of CpG-ODNs on oral tolerance, OVA was coadministered with CpG-ODNs for some studies. Outcomes assessed included cellular airway inflammation, and OVA-specific immunoglobulin levels. Results Oral administration of CpG-ODNs around the time of OVA-sensitization prevented the induction of eosinophilic airway inflammation in a dose-dependent manner. Induction of oral tolerance by the daily administration of high doses (20 mg) of OVA successfully prevented airway inflammation; this was not significantly affected by coadministration of CpG-ODNs. In this model, however, while both conditions suppressed OVA-specific IgG1, only mice that received both CpG-ODNs and OVA demonstrated enhanced IgG2a. In mice with previously-established OVA-induced airway inflammation, only those treated with both OVA and CpG-ODNs (but not treated with either agent alone) demonstrated tolerance to inhaled OVA, manifested by reduced airway. This desensitization also paralleled enhanced IgG2a production Conclusions These findings provide the first indication that oral administration of CpG-ODNs is effective in preventing onset of antigen-induced eosinophilic airway inflammation in murine model of asthma. More importantly, when CpG-ODNs was administered orally with antigen, successive oral tolerance was induced in established eosinophilic airway inflammation.

Inhibition of Th1- and Th2-mediated airway inflammation by the sphingosine 1-phosphate receptor agonist FTY720.

The sphingosine 1-phosphate receptor agonist FTY720 is a novel immunomodulator that sequesters lymphocytes in secondary lymphoid organs and thereby prevents their migration to sites of inflammation. However, there is currently no information available on whether this drug affects Th1 or Th2 cell-mediated lung-inflammatory responses. The effect of FTY720 was therefore investigated in a murine airway inflammation model using OVA-specific, in vitro differentiated, and adoptively transferred Th1 and Th2 cells. Both Th1 and Th2 cells express a similar pattern of FTY720-targeted sphingosine 1-phosphate receptors. The OVA-induced Th1-mediated airway inflammation characterized by increased numbers of lymphocytes and neutrophils in bronchoalveolar lavage fluid was significantly inhibited by oral FTY720 treatment. Similarly, FTY720 suppressed the Th2 cell-induced bronchoalveolar lavage fluid eosinophilia and the infiltration of T lymphocytes and eosinophils into the bronchial tissue. Moreover, the Ag-induced bronchial hyperresponsiveness to inhaled metacholine was almost completely blocked. The inhibitory effect of FTY720 on airway inflammation, induction of bronchial hyperresponsiveness, and goblet cell hyperplasia could be confirmed in an actively Ag-sensitized murine asthma model, clearly indicating that Th2 cell-driven allergic diseases such as asthma could benefit from such treatment.

PPAR-alpha and -gamma but not -delta agonists inhibit airway inflammation in a murine model of asthma: in vitro evidence for an NF-kappaB-independent effect.

1. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that have been proposed to regulate inflammation by antagonising the nuclear factor-kappaB (NF-kappaB) signalling pathway. We investigated the role of PPARs using synthetic agonists in murine models of airway inflammation, and addressed the possible effect on NF-kappaB signalling in vitro using a human epithelial cell line, A549. 2. Sensitised BALB/c mice exposed to an aerosol solution of ovalbumin had an increased number of airway eosinophils, neutrophils and lymphocytes. When given intranasally an hour before the aerosol challenge, a PPAR-alpha (GW 9578) and PPAR-gamma (GI 262570) selective agonist as well as a dual PPAR-alpha/gamma (GW 2331) agonist selectively inhibited allergen-induced bronchoalveolar lavage eosinophil and lymphocyte but not neutrophil influx. In contrast, a PPAR-delta agonist (GW 501516) was inactive. 3. When given intranasally an hour before challenge, PPAR-alpha and PPAR-gamma selective agonists as well as a dual PPAR-alpha/gamma agonist did not inhibit lipopolysaccharide-induced bronchoalveolar lavage neutrophil influx or tumour necrosis factor-alpha (TNF-alpha) and KC production. 4. In A549 cells, selective agonists for PPAR-alpha, -gamma and -delta did not inhibit intracellular adhesion molecule-1 expression following stimulation with proinflammatory cytokines. In addition, IL-8 release and the activation of an NF-kappaB-responsive reporter gene construct were inhibited only at micromolar concentrations, suggesting that these effects were not PPAR-mediated. 5. Our in vivo data show that agonists of PPAR-alpha and -gamma, but not -delta, inhibit allergen-induced bronchoalveolar lavage eosinophil and lymphocyte influx. In vitro data suggest that this effect might not be mediated by antagonism of the NF-kappaB pathway.

A High-Molecular-Weight Mite Antigen (HM1) Fraction Aggravates Airway Hyperresponsiveness of Allergic Mice to House Dusts and Whole Mite Cultures

Background: The house dust mite Dermatophagoides farinae is the most common aeroallergen causing human allergic asthma. Previously, we demonstrated that a high-molecular-weight allergenic fraction (HM1), which was abundant in D. farinae extracts, induced a proliferative response of T cells from healthy donors. The induction was mediated through the activation of macrophages without MHC class II restriction. In this study, we investigate whether HM1 influences the development of airway inflammation in murine models of asthma. Methods: BALB/c mice were injected twice intraperitoneally with D. farinae fecal extract (Dff) at an interval of 5 days. They were exposed daily to aerosolized antigen (group 1: Dff, group 2: HM1, group 3: HM1-depleted Dff and group 4: PBS) for 10 days. The effect of HM1 on their airway inflammation was evaluated by measuring acetylcholine-induced airway hyperresponsiveness and inflammatory cell infiltration in lung tissue. Results: The inhalation of the whole fecal extract or the HM1 fraction induced airway hyperresponsiveness which was detectable after 24 h and was maintained for as long as 120 h. The inhalation of extract depleted of the HM1 fraction induced hyperresponsiveness measured at 24 h but this was not maintained for 120 h. Macrophage infiltration was significantly prolonged in mice inhaling the whole extract and the HM1 fraction compared to the HM1-depleted extract. Conclusion: The inhalation of the high-molecular-weight HM1 fraction of D. farinae prolonged airway hyperresponsiveness and macrophage inflammation in a mouse model of hypersensitivity. The results indicate that the HM1 fraction which can induce T cell proliferation through macrophage activation may play a role in the duration of airway responsiveness.

Construction of single-chain interleukin-12 DNA plasmid to treat airway hyperresponsiveness in an animal model of asthma.

Allergic asthma is strongly associated with the airway inflammation caused by the dysregulated production of cytokines secreted by the allergen-specific type-2 T helper (Th2) cells. Interleukin (IL)-12 is a heterodimeric cytokine, which strongly promotes the differentiation of naive CD4(+) T cells to the type-1 T helper (Th1) phenotype and suppresses the expression of Th2 cytokines. Therefore, immunotherapy with IL-12 has been suggested as a possible therapy for asthma. In previous studies, we developed a murine model of airway inflammation based on the purified, house dust-mite allergen Der p 1 (Dermatophagodies pteronyssinus) as a clinically relevant allergen. We hypothesized that the expression of IL-12 in the airway may represent an effective therapy for allergic airway diseases. In this study, we investigate whether the local transfer of the IL-12 gene to respiratory tissues modifies allergic inflammation and airway hyper-responsiveness (AHR) in our disease model. To enhance the in vivo delivery of the IL-12 gene, we expressed the murine single-chain IL-12 protein from a nonviral vector to which the two IL-12 subunits (p35 and p40) were linked by a 14- to 18-amino-acid linker. One of these single-chain IL-12s, containing an 18 amino-acid polypeptide linker, was stably expressed and had a high level of biological activity comparable to that of native IL-12 in vitro. In mice with Der p 1-induced asthma, the local administration of this IL-12 fusion gene into the lungs significantly prevented the development of AHR, abrogated airway eosinophilia, and inhibited type-2 cytokine production. These findings indicate that the local transfer of the single-chain IL-12 gene is effective in modulating pulmonary allergic responses and may be a convenient method for future applications of DNA vaccination.

Elevated soluble ST2 protein levels in sera of patients with asthma with an acute exacerbation.

Previous studies have reported that ST2 is preferentially expressed on Th2 cells and plays a critical part in controlling airway inflammation in murine models of asthma. However, the clinical role of ST2 in patients with bronchial asthma remains unclear. In our study, we examined 56 patients with atopic asthma in a nonattack phase and 200 nonatopic normal volunteers for healthy control, and analyzed the relationship of their serum ST2 levels to asthma severity, pulmonary function, and laboratory data. Of the 56 patients with atopic asthma, 30 exhibited asthmatic exacerbation, and their serum ST2 levels were also analyzed. The serum ST2 levels were low, but a statistical difference was found between patients with nonattack asthma and the healthy control group (p < 0.05). We also found a differential rise of serum ST2 level that correlates well with the severity of asthma exacerbation. Furthermore, the serum ST2 levels during asthma exacerbation statistically correlated with the percentage of predicted peak expiratory flow (r = -0.634, p = 0.004) and Pa(CO(2)) (r = 0.516, p = 0.003). These results suggest that soluble human ST2 protein in sera may be related to Th2-mediated allergic inflammation inducing acute exacerbation in patients with atopic asthma.

Murine models of airway inflammation.

AbstractThe suitability of any animal model of allergic airway inflammation is assessed by its ability to mimic human asthma. Thus, the ideal model would exhibit early and late antigen-induced airway responses, reversible bronchial hyperresponsiveness, peribronchial eosinophilia, and chronic lung remodeling (1). In this regard, the guinea pig has traditionally been the species of choice for many investigators and has been especially invaluable in elucidating mechanisms governing changes in airway physiology (2). However, in recent years, murine models of allergic airway disease have been extensively employed since the mouse can also be sensitized to a number of different antigens, developing an associated lung inflammatory response. This increased use of the mouse has largely been due to the commercial availability of species-specific reagents, as well as the development of gene knockout mice. In addition, the murine immune system has been relatively well characterized and in practical terms, the mouse is cost effective for experimentation.KeywordsStainless Steel MeshAllergic Airway InflammationAirway ResponseAllergic Airway DiseaseCockroach AllergenThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.