Depletion of CD56+CD3+ invariant natural killer T cells prevents allergen-induced inflammation in humanized mice.

BACKGROUND: CD56-expressing natural killer (NK) cells as well as invariant NK T (iNKT) cells have been shown to either promote or inhibit allergic immune responses. OBJECTIVE: The aim of the present study was to investigate the impact of these cells in a recently developed humanized mouse model of allergen-induced IgE-dependent gut and lung inflammation. METHODS: Nonobese diabetic-severe combined immunodeficiency γ-chain knockout mice were injected intraperitoneally with human PBMCs or CD56-depleted (CD56neg) PBMCs from highly sensitized donors with birch or grass pollen allergy together with the respective allergen or with NaCl as a control. Three weeks later, the mice were challenged with the allergen rectally and gut inflammation was monitored by video miniendoscopy and by histology. Furthermore, airway inflammation was measured after an additional intranasal allergen challenge. RESULTS: Allergen-specific human IgE in mouse sera, detectable only after coinjection of the respective allergen, was reduced in mice being injected with CD56neg PBMCs compared with in mice receiving nondepleted PBMCs. Consequently, allergen-induced IgE-dependent colitis, airway hyperreactivity, and mucus-producing goblet cells were significantly inhibited in these mice. Interestingly, reconstitution of CD56neg PBMCs with nondepleted CD56+ cells and with CD56+CD3+ iNKT cells restored gut as well as lung inflammation, whereas addition of CD3-depleted CD56+ cells did not. CONCLUSION: These results demonstrate that allergen-specific gut and lung inflammation in PBMC-engrafted humanized mice is promoted by CD56+CD3+ iNKT cells, which opens new possibilities of therapeutic intervention in allergic diseases.

Cordyceps polysaccharide ameliorates airway inflammation in an ovalbumin-induced mouse model of asthma via TGF-ß1/Smad signaling pathway.

Allergic asthma is a chronic inflammatory disease characterized by airflow obstruction, airway hyperresponsiveness (AHR), airway inflammation, and mucus overproduction. Cordyceps polysaccharide (CPS) is one of the main bioactive compounds of Cordyceps militarisis, a traditional Chinese medicine. In this study, we established a mouse model of asthma using ovalbumin (OVA) challenge and evaluated the potential regulatory effect of CPS (25, 50, and 100 mg/kg) on asthmatic mice. These results showed that the asthmatic mice treated with CPS suppressed the secretion of eotaxin, IL-4, IL-5, IL-13, and IFN-γ in the blood and bronchoalveolar lavage fluid (BALF), and decreased serum IgE levels compared to the vehicle-treated mice. CPS also alleviated inflammatory cell infiltration, goblet cell hyperplasia, and the increases of inflammatory cells in the mouse model of asthma. In addition, OVA-induced AHR was inhibited by CPS treatment. Further analyses of protein expression revealed that CPS inhibited the activation of transforming growth factor ß1 (TGF-ß1)/Smad pathway in mice with asthma. These findings indicated that CPS might serve as a potential therapeutic agent for the management of allergic asthma.

Acupuncture Regulates the Balance of CD4+ T Cell Subtypes in Experimental Asthma Mice.

OBJECTIVE: To evaluate the involvement of different CD4+ T cell subtypes in the anti-asthmatic effects of acupuncture in asthmatic mice. METHODS: BALB/c mice were challenged by ovalbumin (OVA) for the establishment of experimental asthma model. Mice were divided into 4 groups by a random number table including the normal control, asthma model, acupuncture and sham acupuncture groups (14 per group). Acupoints Dazhui (GV 14), bilateral Fengmen (BL 12) and Feishu (BL 13) were selected for manual acupuncture treatment every other day for 4 weeks and Huantiao (GB 30) was selected for sham acupuncture. Airway hyperresponsiveness was examined by Buxco Pulmonary System. Pulmonary histopathology analysis was performed for inflammatory cell infiltration and mucus hypersecretion by haematoxylin eosin staining and periodic acid-Schiffstaining. Inflammatory mediators assays of serum were investigated by enzyme-linked immunosorbent assay and Bio-Plex. CD4+ T cell subpopulations including the expression levels of important factors in T lymphocyte polarization in lung tissue were examined by flow cytometric and Western blot analyses. Related pathways were detected by Western blot assay. RESULTS: Compared with the OVA-induced asthma model group, acupuncture could attenuate airway hyperresponsiveness, inhibit inflammatory cell infiltration and mucus hypersecretion (P<0.05 or P<0.01). Furthermore, acupuncture increased the expressions of T-bet and Foxp3+, the cell numbers of CD4+ interferon gamma (IFN-γ)+ and CD4+ Foxp3+ in lung tissue and the level of Treg type cytokine interleukin (IL)-10 in serum (P<0.05 or P<0.01). Meanwhile, acupuncture reduced the RAR-related orphan receptor gamma t (RORγt) level, the cell numbers of CD4+ IL-17A+ as well as the levels of IL-5, IL-13 and IL-17A in serum (P<0.05 or P<0.01). In addition, both acupuncture and sham acupuncture could inhibit the phosphorylation of p38 and p44/42 (P<0.01). CONCLUSION: Acupuncture could alleviate allergic airway inflammation by strengthening the activities of Th1 and Treg, thus regulating the balance of CD4+ T cell subtypes in experimental asthmatic mice.

The Protective Effects of 2,3,5,4'-Tetrahydroxystilbene-2-O-ß-d-Glucoside in the OVA-Induced Asthma Mice Model.

Asthma is an inflammatory disease caused by an imbalance of Th1 and Th2 cells. In general, asthma is characterized by a stronger Th2 response. Most conventional asthma treatment focuses on improving airway flow or suppression of airway inflammation. To reduce the side effects of currently used asthma medicines, we have conducted studies on natural products that have no side effects. 2,3,5,4'-tetrahydroxystilbene-2-O-ß-d-glucoside (TSG), the main compound of Polygonum multiflorum (PM), has various biological activities, including anti-inflammation and anti-oxidation activities. However, the effect of TSG on asthma has not been studied yet. We examined the effects of TSG on Th2 immune responses using an OVA-induced asthma animal model. OVA-sensitized mice were treated with TSG. 24 h after the last intranasal challenge, airway hyperresponsiveness (AHR) was measured or serum and bronchoalveolar lavage fluid (BALF) were harvested. We measured typical Th1 and Th2 cytokines in serum and BALF. As a result, TSG suppressed Th2 responses, as shown by the lower levels of IL-4, IL-5, total IgE, OVA-specific IgE, and OVA-specific IgG1. On the other hand, TSG increased Th1 responses, as shown by the levels of IFN-gamma. Collectively, these results confirm the potential of TSG for asthma treatment through modulation of inflammatory responses. Considering that the cytotoxic effect of PM extract is due to the cis isomer of TSG, if the effect of TSG on asthma treatment is found to be non-toxic in clinical trials, it would be more effective to use it as a purified component than PM extract as an asthma treatment agent.

Prophylactic effect of rosmarinic acid on tracheal responsiveness, white blood cell count and oxidative stress markers in lung lavage of sensitized rats.

BACKGROUND: Rosmarinic acid (RA) as an active component of several medicinal plants, has shown anti-inflammatory and anti-oxidant effects. In this study, the effect of RA on tracheal responsiveness (TR), lung inflammatory cells, oxidant biomarkers in sensitized rats were evaluated. METHODS: TR to methacholine and ovalbumin (OVA) as well as total and differential white blood cell (WBC) count and levels of nitrogen dioxide, nitrate, malondialdehyde, thiol, superoxide dismutase, and catalase in bronchoalveolar lavage fluid were measured in control (group C) rats, sensitized animals to OVA and given drinking water alone (group S), S groups receiving drinking water containing three concentrations of RA (0.125, 0.250 and 0.500 mg/mL) and dexamethasone (1.25 µg/mL), (n = 6 in each group). RESULTS: Increased TR to methacholine and OVA, total WBC count, percentages of eosinophils, monocytes, neutrophils and levels of oxidant biomarkers but decreased other measured parameters were observed in group S compared to group C. Percentages of lymphocytes and antioxidant biomarkers were significantly increased but other measured parameters were significantly decreased in S group treated with dexamethasone and in rats treated with the two higher concentrations of RA compared to S group. The effect of RA medium concentration on percentage of eosinophils and RA high concentration on total WBC count and percentages of eosinophils and lymphocytes, were significantly higher than those of dexamethasone. CONCLUSION: These results showed the concentration-dependent effect of RA on tracheal responses, lung inflammatory cells and oxidant-antioxidant parameters which was comparable to that of dexamethasone at used concentrations in sensitized rats.

Respiratory Allergic Disorders.

Allergic asthma refers to a chronic reversible bronchoconstriction influenced by an allergic trigger, leading to symptoms of cough, wheezing, shortness of breath, and chest tightness. Allergic bronchopulmonary aspergillosis is a complex hypersensitivity reaction, often in patients with asthma or cystic fibrosis, occurring when bronchi become colonized by Aspergillus species. The clinical picture is dominated by asthma complicated by recurrent episodes of bronchial obstruction, fever, malaise, mucus production, and peripheral blood eosinophilia. Hypersensitivity pneumonitis is a syndrome associated with lung inflammation from the inhalation of airborne antigens, such as molds and dust.

Reduction of Endogenous Melatonin Accelerates Cognitive Decline in Mice in a Simulated Occupational Formaldehyde Exposure Environment.

Individuals afflicted with occupational formaldehyde (FA) exposure often suffer from abnormal behaviors such as aggression, depression, anxiety, sleep disorders, and in particular, cognitive impairments. Coincidentally, clinical patients with melatonin (MT) deficiency also complain of cognitive problems associated with the above mental disorders. Whether and how FA affects endogenous MT metabolism and induces cognitive decline need to be elucidated. To mimic occupational FA exposure environment, 16 healthy adult male mice were exposed to gaseous FA (3 mg/m³) for 7 consecutive days. Results showed that FA exposure impaired spatial memory associated with hippocampal neuronal death. Biochemical analysis revealed that FA exposure elicited an intensive oxidative stress by reducing systemic glutathione levels, in particular, decreasing brain MT concentrations. Inversely, intraperitoneal injection of MT markedly attenuated FA-induced hippocampal neuronal death, restored brain MT levels, and reversed memory decline. At tissue levels, injection of FA into the hippocampus distinctly reduced brain MT concentrations. Furthermore, at cellular and molecular levels, we found that FA directly inactivated MT in vitro and in vivo. These findings suggest that MT supplementation contributes to the rescue of cognitive decline, and may alleviate mental disorders in the occupational FA-exposed human populations.

Vitamin D Supplementation Reduces Induction of Epithelial-Mesenchymal Transition in Allergen Sensitized and Challenged Mice.

Asthma is a chronic disease of the lung associated with airway hyperresponsiveness (AHR), airway obstruction and airway remodeling. Airway remodeling involves differentiation of airway epithelial cells into myofibroblasts via epithelial-mesenchymal transition (EMT) to intensify the degree of subepithelial fibrosis. EMT involves loss in E-cadherin with an increase in mesenchymal markers, including vimentin and N-cadherin. There is growing evidence that vitamin D has immunomodulatory and anti-inflammatory properties. However, the underlying molecular mechanisms of these effects are still unclear. In this study, we examined the contribution of vitamin D on the AHR, airway inflammation and expression of EMT markers in the airways of mice sensitized and challenged with a combination of clinically relevant allergens, house dust mite, ragweed, and Alternaria (HRA). Female Balb/c mice were fed with vitamin D-sufficient (2000 IU/kg) or vitamin D-supplemented (10,000 IU/kg) diet followed by sensitization with HRA. The density of inflammatory cells in the bronchoalveolar lavage fluid (BALF), lung histology, and expression of EMT markers by immunofluorescence were examined. Vitamin D-supplementation decreased AHR, airway inflammation in the BALF and the features of airway remodeling compared to vitamin D-sufficiency in HRA-sensitized and -challenged mice. This was accompanied with increased expression of E-cadherin and decreased vimentin and N-cadherin expression in the airways. These results indicate that vitamin D may be a beneficial adjunct in the treatment regime in allergic asthma.

The MIF Antagonist ISO-1 Attenuates Corticosteroid-Insensitive Inflammation and Airways Hyperresponsiveness in an Ozone-Induced Model of COPD.

INTRODUCTION: Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine associated with acute and chronic inflammatory disorders and corticosteroid insensitivity. Its expression in the airways of patients with chronic obstructive pulmonary disease (COPD), a relatively steroid insensitive inflammatory disease is unclear, however. METHODS: Sputum, bronchoalveolar lavage (BAL) macrophages and serum were obtained from non-smokers, smokers and COPD patients. To mimic oxidative stress-induced COPD, mice were exposed to ozone for six-weeks and treated with ISO-1, a MIF inhibitor, and/or dexamethasone before each exposure. BAL fluid and lung tissue were collected after the final exposure. Airway hyperresponsiveness (AHR) and lung function were measured using whole body plethysmography. HIF-1α binding to the Mif promoter was determined by Chromatin Immunoprecipitation assays. RESULTS: MIF levels in sputum and BAL macrophages from COPD patients were higher than those from non-smokers, with healthy smokers having intermediate levels. MIF expression correlated with that of HIF-1α in all patients groups and in ozone-exposed mice. BAL cell counts, cytokine mRNA and protein expression in lungs and BAL, including MIF, were elevated in ozone-exposed mice and had increased AHR. Dexamethasone had no effect on these parameters in the mouse but ISO-1 attenuated cell recruitment, cytokine release and AHR. CONCLUSION: MIF and HIF-1α levels are elevated in COPD BAL macrophages and inhibition of MIF function blocks corticosteroid-insensitive lung inflammation and AHR. Inhibition of MIF may provide a novel anti-inflammatory approach in COPD.

Mining Novel Allergens from Coconut Pollen Employing Manual De Novo Sequencing and Homology-Driven Proteomics.

Coconut pollen, one of the major palm pollen grains is an important constituent among vectors of inhalant allergens in India and a major sensitizer for respiratory allergy in susceptible patients. To gain insight into its allergenic components, pollen proteins were analyzed by two-dimensional electrophoresis, immunoblotted with coconut pollen sensitive patient sera, followed by mass spectrometry of IgE reactive proteins. Coconut being largely unsequenced, a proteomic workflow has been devised that combines the conventional database-dependent analysis of tandem mass spectral data and manual de novo sequencing followed by a homology-based search for identifying the allergenic proteins. N-terminal acetylation helped to distinguish "b" ions from others, facilitating reliable sequencing. This led to the identification of 12 allergenic proteins. Cluster analysis with individual patient sera recognized vicilin-like protein as a major allergen, which was purified to assess its in vitro allergenicity and then partially sequenced. Other IgE-sensitive spots showed significant homology with well-known allergenic proteins such as 11S globulin, enolase, and isoflavone reductase along with a few which are reported as novel allergens. The allergens identified can be used as potential candidates to develop hypoallergenic vaccines, to design specific immunotherapy trials, and to enrich the repertoire of existing IgE reactive proteins.

Echinacea complex--chemical view and anti-asthmatic profile.

ETHNOPHARMACOLOGICAL RELEVANCE: Echinacea purpurea (L.) Moench is one of the mostly used herbs in the traditional medicine for the treatment of respiratory diseases. Modern interest in Echinacea is directed to its immunomodulatory activity. Recent studies have shown that secretion of asthma-related cytokines in the bronchial epithelial cells can be reversed by Echinacea preparations. AIM OF THE STUDY: To examine the pharmacodynamics profile of Echinacea active principles, a complex has been isolated from its flowers by alkaline extraction and has been tested using an animal model of allergic asthma. MATERIAL AND METHODS: The structural features of Echinacea purpurea complex was determined using chemical and spectroscopic methods. Allergic inflammation of the airways was induced by repetitive exposure of guinea pigs to ovalbumin. Echinacea complex was then administered 14 days in 50mg/kg b.w. daily dose perorally. Bronchodilatory effect was verified as decrease in the specific airway resistance (sRaw) in vivo and by reduced contraction amplitude (mN) of tracheal and pulmonary smooth muscle to cumulative concentrations of acetylcholine and histamine in vitro. The impact on mucociliary clearance evaluated measurement of ciliary beat frequency (CBF) in vitro using LabVIEW™ Software. Anti-inflammatory effect of Echinacea complex was verified by changes in exhaled NO levels and by Bio-Plex® assay of Th2 cytokine concentrations (IL-4, IL-5, IL-13 and TNF-alpha) in serum and bronchoalveolar lavage fluid (BALF). RESULTS: Chemical and spectroscopic studies confirmed the presence of carbohydrates, phenolic compounds and proteins, as well as the dominance of rhamnogalacturonan and arabinogalactan moieties in Echinacea complex. The significant decrease in sRaw values and suppressed histamine and acetylcholine-induced contractile amplitude of isolated airways smooth muscle that were similar to effects of control drug salbutamol confirmed Echinacea complex bronchodilatory activity. The anti-inflammatory effect was comparable with that of control agent budesonide and was verified as significantly reduced exhaled NO levels and concentration of Th2 cytokines in serum and BALF. The values of CBF were changed only insignificantly on long-term administration of Echinacea complex suggested its minimal negative impact on mucociliary clearance. CONCLUSION: Pharmacodynamic studies have confirmed significant bronchodilatory and anti-inflammatory effects of Echinacea complex that was similar to effects of classic synthetic drugs. Thus, results provide a scientific basis for the application of this herb in traditional medicine as a supplementary treatment of allergic disorders of the airways, such as asthma.

An Enzymatically Active ß-1,3-Glucanase from Ash Pollen with Allergenic Properties: A Particular Member in the Oleaceae Family.

Endo-ß-1,3-glucanases are widespread enzymes with glycosyl hydrolitic activity involved in carbohydrate remodelling during the germination and pollen tube growth. Although members of this protein family with allergenic activity have been reported, their effective contribution to allergy is little known. In this work, we identified Fra e 9 as a novel allergenic ß-1,3-glucanase from ash pollen. We produced the catalytic and carbohydrate-binding domains as two independent recombinant proteins and characterized them from structural, biochemical and immunological point of view in comparison to their counterparts from olive pollen. We showed that despite having significant differences in biochemical activity Fra e 9 and Ole e 9 display similar IgE-binding capacity, suggesting that ß-1,3-glucanases represent an heterogeneous family that could display intrinsic allergenic capacity. Specific cDNA encoding Fra e 9 was cloned and sequenced. The full-length cDNA encoded a polypeptide chain of 461 amino acids containing a signal peptide of 29 residues, leading to a mature protein of 47760.2 Da and a pI of 8.66. An N-terminal catalytic domain and a C-terminal carbohydrate-binding module are the components of this enzyme. Despite the phylogenetic proximity to the olive pollen ß-1,3-glucanase, Ole e 9, there is only a 39% identity between both sequences. The N- and C-terminal domains have been produced as independent recombinant proteins in Escherichia coli and Pichia pastoris, respectively. Although a low or null enzymatic activity has been associated to long ß-1,3-glucanases, the recombinant N-terminal domain has 200-fold higher hydrolytic activity on laminarin than reported for Ole e 9. The C-terminal domain of Fra e 9, a cysteine-rich compact structure, is able to bind laminarin. Both molecules retain comparable IgE-binding capacity when assayed with allergic sera. In summary, the structural and functional comparison between these two closely phylogenetic related enzymes provides novel insights into the complexity of ß-1,3-glucanases, representing a heterogeneous protein family with intrinsic allergenic capacity.

Critical role for syndecan-4 in dendritic cell migration during development of allergic airway inflammation.

Syndecan-4 (SDC4), expressed on dendritic cells (DCs) and activated T cells, plays a crucial role in DC motility and has been shown as a potential target for activated T-cell-driven diseases. In the present study, we investigate the role of SDC4 in the development of T-helper 2 cell-mediated allergic asthma. Using SDC4-deficient mice or an anti-SDC4 antibody we show that the absence or blocking of SDC4 signalling in ovalbumin-sensitized mice results in a reduced asthma phenotype compared with control animals. Most importantly, even established asthma is significantly decreased using the anti-SDC4 antibody. The disturbed SDC4 signalling leads to an impaired motility and directional migration of antigen-presenting DCs and therefore, to a modified sensitization leading to diminished airway inflammation. Our results demonstrate that SDC4 plays an important role in asthma induction and indicate SDC4 as possible target for therapeutic intervention in this disease.

Pollen-derived adenosine is a necessary cofactor for ragweed allergy.

BACKGROUND: Ragweed (Ambrosia artemisiifolia) is a strong elicitor of allergic airway inflammation with worldwide increasing prevalence. Various components of ragweed pollen are thought to play a role in the development of allergic responses. The aim of this study was to identify critical factors for allergenicity of ragweed pollen in a physiological model of allergic airway inflammation. METHODS: Aqueous ragweed pollen extract, the low molecular weight fraction or the major allergen Amb a 1 was instilled intranasally on 1-11 consecutive days, and allergic airway inflammation was evaluated by bronchoalveolar lavage, lung histology, serology, gene expression in lung tissue, and measurement of lung function. Pollen-derived adenosine was removed from the extract enzymatically to analyze its role in ragweed-induced allergy. Migration of human neutrophils and eosinophils toward supernatants of ragweed-stimulated bronchial epithelial cells was analyzed. RESULTS: Instillation of ragweed pollen extract, but not of the major allergen or the low molecular weight fraction, induced specific IgG1 , pulmonary infiltration with inflammatory cells, a Th2-associated cytokine signature in pulmonary tissue, and impaired lung function. Adenosine aggravated ragweed-induced allergic lung inflammation. In vitro, human neutrophils and eosinophils migrated toward supernatants of bronchial epithelial cells stimulated with ragweed extract only if adenosine was present. CONCLUSIONS: Pollen-derived adenosine is a critical factor in ragweed-pollen-induced allergic airway inflammation. Future studies aim at therapeutic strategies to control these allergen-independent pathways.

Does climate therapy at moderate altitudes improve pulmonary function in asthma patients? A systematic review.

PURPOSE: Allergic bronchial asthma is one of the most common chronic diseases worldwide. For many years, the climate at moderate altitude has been used as an alternative therapy for patients suffering from bronchial asthma. The aim of such therapy is to reduce the medication dose and to improve the quality of life for each patient. The aim of our current work was to assess published data evaluating the effects of climate therapy at moderate altitude on the health status of patients with bronchial asthma. The health status is represented through surrogate parameters for the pulmonary function (forced expiratory volume in one second (FEV1)), bronchial hyperresponsiveness (PC20), and inflammation (total number of eosinophils, eosinophilic cationic protein, and exhaled nitric oxide). METHODS: Our systematic review included randomized controlled trials (RCTs) and single-armed studies with adults and children participating. Included in our review were climate therapies occurring at moderate altitudes between 1,500 and 2,500 m and evaluation of patient FEV1 or PC20 values. RESULTS: A literature research in MEDLINE and EMBASE identified three RCTs, two clinically controlled trials, and 15 single-armed studies. Analysis revealed a lack of evidence regarding the moderate altitude therapy arising from small sample sizes, deficits in documentation, and heterogeneous results. Most of the studies, however, showed a tendency for improvement of the analyzed parameters. CONCLUSIONS: The currently available data do not allow for valid and generalizable recommendations with respect to moderate altitude therapy for patients with allergic bronchial asthma. There is a need for additional, qualitatively strong research including larger sample sizes and randomized, controlled trial design.

The effect of the extract of Crocus sativus on tracheal responsiveness and plasma levels of IL-4, IFN-γ, total NO and nitrite in ovalbumin sensitized guinea-pigs.

UNLABELLED: ETHNOMEDICAL RELEVANCE: Anti-inflammatory, anti oxidant and effect of Crocus sativus (C. sativus) on Th1/Th2 balance were described previously. AIM OF THE STUDY: The preventive effects of the extract of Crocus sativus on tracheal responsiveness and plasma levels of IL-4, IFN-γ, total NO and nitrite were examined on sensitized guinea pigs. MATERIALS AND METHODS: Five groups of sensitized guinea pigs to ovalbumin (OVA), were given drinking water containing three concentrations of the extract of Crocus sativus, dexamethasone (S+D) or alone (group S). Tracheal responses (TR) of control animals (group C) and sensitized guinea pigs (n=6, for each group) to methacholine, OVA and the levels of IL-4, IFN-γ, total NO and nitrite in serum were examined. RESULTS: The TR to both methacholine and OVA, the levels of serum IL-4, total NO and nitrite in S guinea pigs were significantly increased but that of IFN-γ and IFN-γ/IL-4 ratio (Th1/Th2 balance) were decreased compared to the controls (p<0.05 to p<0.001). In the treated animals with dexamethasone and all concentrations of the extract, TR to both methacholine and OVA, IL-4, total NO and nitrite were significantly decreased but IFN-γ and IFN-γ/IL-4 ratio increased compared to S group (p<0.05 to p<0.001). The effects of the highest concentration of the extract was greater than those of other concentrations and the effect of dexamethasone (p<0.05 to p<0.01). CONCLUSIONS: These results not only showed a preventive effect of C. sativus extract on tracheal responses and serum levels of inflammatory mediators in sensitized guinea pigs but also showed increased Th1/Th2 balance.

Effectiveness of Cissampelos sympodialis and its isolated alkaloid warifteine in airway hyperreactivity and lung remodeling in a mouse model of asthma.

BACKGROUND: Cissampelos sympodialis Eichl. (Menispermaceae) is a plant found in Northeastern and Southeast of Brazil and hot water infusion of C. sympodialis root bark is largely used in the indigenous and folk medicine to treat several inflammatory disorders, including asthma. Asthma is a chronic inflammatory allergic disease characterized by airway hyperreactivity (AHR), eosinophil tissue infiltration and lung remodeling. The aim of this study was to evaluate the therapeutic effect of C. sympodialis and its isolated alkaloid warifteine on allergen triggered airway hyperreactivity (AHR) and lung remodeling in murine model of asthma. METHODOLOGY/PRINCIPAL FINDINGS: The oral pre-treatment with C. sympodialis or warifteine inhibited allergen-induced AHR to inhaled methacholine and IL-13 levels in the bronchoalveolar lavage (BAL). In order to investigate the therapeutic potential of C. sympodialis and warifteine, animals were treated 1h after the last ovalbumin (OVA) challenge in sensitized animals. Similarly to the pre-treatment, post-treatment with warifteine was effective to inhibit significantly AHR to inhaled methacholine and to reduce IL-13 levels in the BAL. In addition, oral pre- or post-treatments with C. sympodialis or warifteine reduced OVA-induced eosinophil tissue infiltration, mucus production and subepithelial fibrosis to values similar to nonallergic controls. CONCLUSIONS: Our data show the anti-allergic and immunoregulatory properties of C. sympodialis, acting mostly through the active compound warifteine, to inhibit the airway hyperreactivity and lung remodeling through a mechanism at least partially dependent of IL-13 and eosinophil inhibition. Therefore placing warifteine as an interesting therapeutic candidate in allergic inflammation and corroborating the folk medicine use of C. sympodialis as anti-allergic plant.

Lyprinol reduces inflammation and improves lung function in a mouse model of allergic airways disease.

BACKGROUND: Asthma is an inflammatory airway disease that is characterized by an influx of eosinophils to the lungs, mucus hypersecretion and T helper type 2 cytokine production. Recent dietary changes, including a decreased ω-3 polyunsaturated fatty acid (PUFA) intake, may have contributed to increased asthma rates and dietary supplementation with marine oil could have clinical benefits. OBJECTIVE: To assess the effects of dietary supplementation with ω-3 PUFAs on allergic inflammation and lung function using a mouse model of ovalbumin (OVA)-induced allergic airway disease (AAD). METHODS: BALB/c mice received a daily supplement of either fish oil (rich in ω-3 PUFA) or lyprinol (a complex mixture of various marine lipids plus vitamin E and olive oil) before and during AAD. The effects of supplementation on AAD were assessed. RESULTS: Lyprinol but not fish oil treatment reduced eosinophil influx into the bronchoalveolar lavage fluid, the lung tissue surrounding the airways and the blood, decreased mucus hypersecretion in the lung and reduced airway hyperresponsiveness (AHR). The effects of lyprinol were not associated with changes in serum IgG1 or IgG2a, or the release of IL-4, IL-5, IL-13 and IFN-γ. CONCLUSIONS: Lyprinol suppresses the development of allergic inflammation and AHR in AAD. The therapeutic potential of dietary supplementation with lyprinol for asthma warrants further investigation.

Sensitization to inhaled ryegrass pollen by collateral priming in a murine model of allergic respiratory disease.

BACKGROUND: Mouse models of asthma suffer from the necessity to prime the animals by injections before respiratory exposure. Our aim was to develop a mouse model that mimics the progression of human allergic disease upon low-dose inhaled allergen exposure. METHODS: Mice were primed intraperitoneally to ovalbumin (OVA) before they were exposed repeatedly to aerosols of either OVA, ryegrass (Lolium perenne) pollen extract, or both concomitantly. The sensitization to ryegrass pollen proteins was evaluated by measurement of specific serum antibody, by the respiratory response to a challenge with ryegrass pollen extract and by lung cytokine production after challenge. RESULTS: Inhalation of ryegrass pollen extract alone did not result in sensitization. Sensitization to inhaled ryegrass pollen proteins, however, did occur in mice that had been sensitized to OVA by intraperitoneal injections and were then exposed to inhaled ryegrass pollen extract and OVA simultaneously. T and B cell priming was ascertained by ryegrass pollen-specific IgG1 and IgE antibody production and by induction of airway inflammation and of Th2 cytokine mRNA transcripts in the lungs upon airway challenge with ryegrass pollen extract. A progressive spread of the IgE/IgG1 response to different ryegrass pollen proteins could be visualized in immunoblots by comparing antibody patterns at day 56 and 86. CONCLUSIONS: Low-dose inhalatory allergen exposure results in sensitization when airways are exposed at the same time to another allergen to which the animals are already sensitized. This model can help to unravel the mechanisms that underlie the development and progression of respiratory allergic diseases.

Role of pollen allergy in Taiwanese patients with allergic rhinitis.

BACKGROUND/PURPOSE: Pollen allergy is believed to be less common in East Asia, Latin America, and tropical areas. The purpose of this study was to understand the role of pollen allergy in Taiwan. METHODS: Patients with clinically diagnosed allergic rhinitis were enrolled. All subjects received a 30-item skin test panel that included perennial allergens (house dust mix, Dermatophagoides pteronyssinus, Dermatophagoides farinae, dog epithelium, cat hairs, cockroach mix, and Candida albicans) and pollen allergens (acacia, pine mix, eucalyptus, beefwood, juniper mix, willow, mulberry mix, pepper tree, cedar, Johnson grass, Bermuda grass, ragweed mix, Timothy grass, spiny pigweed, cocklebur, sage mix, sheep sorrel, dog fennel, pigweed mix, English plantain, castor bean, alfalfa, and dandelion). RESULTS: A total of 419 patients were recruited. A total of 313 (74.7%) had a positive skin test. A total of 288 patients (68.7%) were sensitive to perennial allergens, and 11 8 patients (28.2%) were sensitive to pollen allergens. However, 93 pollen-sensitive patients were also sensitive to perennial allergens, and only 25 were sensitive to pollen allergens alone. The most common allergens were D. pteronyssinus, D. farinae, house dust mix, and cockroach, but the most common pollen allergens were spiny pigweed, Johnson grass, and sheep sorrel. All nasal symptoms tended to be more severe in patients who were sensitive to perennial allergens than in those who were sensitive to pollen allergens alone. CONCLUSION: Most patients with allergic rhinitis in Taiwan are sensitive to perennial allergens, and pollens are a less common allergen.