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  • 1
    Electronic Resource
    Electronic Resource
    Periarticular tissue levels of cytokine- and endothelin-1-like immunoreactivity during the course of antigen-induced arthritis in the rat (1999)
    Springer
    Inflammation research 48 (1999), S. 491-496 
    Details
    ISSN: 1420-908X
    Keywords: Key words: Arthritis — Cytokine — Endothelin — Pannus — Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Objective and Design: To correlate the changes in periarticular tissue levels of pro-inflammatory cytokines and endothelin-1 (ET-1) to local pathophysiology in rats with antigen-induced arthritis (AIA).¶Materials: The periarticular soft tissue was excised from sixty-six rats at different stages of AIA.¶Methods: The samples were homogenized and the levels of immune like (LI) reactivities were determined. The levels in the arthritic joints were compared to those in non-arthritic tissue. Statistical significance was determined by ANOVA followed by Fisher PLSD.¶Results: Compatible with a role in an early alarm reaction some mediators (tumor necrosis factor α-LI, interleukin-2-LI and interferon-γ-LI) were elevated prior to the vascular inflammatory activity. The curve for ET-1-LI closely followed the intensity of the inflammation whereas these parameters preceeded the elevation of interleukin-1β-LI.¶Conclusions: Transient waves of different mediators appear during the course of the arthritis. This indicates the presence of active downregulatory mechanisms. Here the model could differ from human rheumatoid arthritis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s000110050492
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  • 2
    Electronic Resource
    Electronic Resource
    Molecular cloning, expression, and purification of pig interleukin-5 (2000)
    Springer
    Immunogenetics 51 (2000), S. 59-64 
    Details
    ISSN: 1432-1211
    Keywords: Key words Pig ; RACE-PCR ; IL-5 cDNA sequence ; Protein expression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Interleukin-5 (IL-5) is thought to be a key cytokine in allergic inflammation. Pig IL-5 was cloned, sequenced, and expressed to enable us to study of the biological role of IL-5 in pigs used in a model for allergen-induced late-phase reactions. These pigs were sensitized to proteins extracted from Ascaris suum, resulting in hypersensitivity to this antigen in both the skin and airways, and a slight blood eosinophilia. Peripheral blood mononuclear cells from antigen-sensitized pigs were isolated and polyclonally stimulated. Total RNA was extracted and reverse transcribed into cDNA. IL-5 primers based on the cow IL-5 cDNA sequence were used to obtain an initial polymerase chain reaction product. 3′ rapid amplification of cDNA ends (3′RACE) and 5′RACE procedures were applied to identify the 3′ and 5′ ends, respectively. The full-length pig IL-5 cDNA is 405 base pairs long. Mature pig IL-5 was expressed in Escherichia coli with a His-tag for purification. The IL-5 protein is 115 amino acids long, has an estimated molecular weight of 14 000 M r and forms a biologically active homodimer of 28 000 M r . Pig IL-5 shows 65% amino acid identity to the human IL-5 sequence and 90, 88, 83, 62, and 61% identity to the cow, sheep, horse, mouse, and rat counterparts.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050009
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  • 3
    Electronic Resource
    Electronic Resource
    Exhaled nitric oxide: relation to sensitization and respiratory symptoms (2004)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 34 (2004), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Conflicting data have been presented as to whether nitric oxide (NO) in exhaled air is merely reflecting atopy rather than airway inflammation.Objective To investigate the relationship between exhaled NO (eNO) and nasal NO (nNO), respiratory symptoms, and atopy, in the context of a cross-sectional study of the respiratory health of bleachery workers.Methods Two hundred and forty-six non-smoking bleachery and paper-mill workers answered a questionnaire and were examined by measurements of eNO and nNO and spirometry, outside the pollen season. Blood samples were collected and analysed for specific IgE against common aeroallergens (birch, timothy, cat and house dust mite). Atopy was defined as a positive Phadiatop™ test.Results The atopic and the non-atopic subjects without asthma or rhinitis had similar levels of eNO. Subjects reporting asthma or rhinitis who were also sensitized to perennial allergens had higher levels of eNO, whereas those sensitized to only seasonal allergens had similar eNO levels as non-atopic subjects with asthma or rhinitis. In multiple linear regression models adjusted for nNO, eNO was associated with asthma and sensitization to perennial allergens.Conclusion The results indicate that only atopic subjects who have recently been exposed to the relevant allergen have elevated levels of eNO. Atopic subjects who are not being exposed to a relevant allergen or have never experienced symptoms of asthma or rhinitis show normal eNO. These data indicate that eNO relates to airway inflammation in atopic subjects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.2004.01888.x
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  • 4
    Electronic Resource
    Electronic Resource
    Influence of endogenous cortisol on eosinophil function in sensitized pigs: direct measurements of eosinophil peroxidase (1996)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 26 (1996), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background and Objectives Eosinophils are associated with bronchial asthma, but the role of the eosinophil is not fully understood. This study was initiated in order to study the influence of endogenous cortisol on eosinophil recruitment and activation in allergic inflammation in the lower airways in the pig.Methods Polyclonal and monoclonal antibodies against porcine eosinophil peroxidase (EPO) were raised. Detection of eosinophils in blood smears and lung biopsy specimens was achieved using the polyclonal antibody. For determination of porcine EPO in bronchoalveoiar lavage (BAL) fluid, a sandwich enzyme-linked immuno-sorbent assay (ELISA) with a detection limit of 0.15μig/L was developed. No cross-reactivity with porcine myeloperoxidase was found. Pigs that had been actively sensitized with repeated subcutaneous injections of Ascaris suum antigen were acutely challenged with antigen in the lower airways under pentobarbitone anaesthesia.Results Control animals with plasma cortisol levels of approximately 400 nM did not exhibit infiltration of eosinophils into lung parenchyma or EPO-release in the bronchial lumen within 8 h after challenge. However, in pigs treated with a cortisol-synthesis inhibitor (metyrapone), resulting in plasma cortisol levels of approximately 40 nM, there was a marked eosinophil infiltration into lung tissue at 8 h. Furthermore, EPO levels in BAL fluid were increased in some, although not all, low-cortisol animals. There was no infiltration of eosinophils into skin tissue in these animals.Conclusions It is concluded that, after allergen challenge in the lower airways of metyrapone-treated pigs, newly recruited eosinophils infiltrate lung tissue specifically. Furthermore, a cortisol-sensitive release of the eosinophil-derived cationic protein EPO, into the bronchial lumen was established. This is, to our knowledge, the first description of direct measurements of the release of an eosinophil granule protein in a large animal model of allergy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1996.tb00564.x
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  • 5
    Electronic Resource
    Electronic Resource
    Granulocyte function in the airways of allergen-challenged pigs: effects of inhaled and systemic budesonide (1996)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 26 (1996), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Backgroumd Late airways obstruction and eosinophil infiltration after allergen challenge are often seen in human asthma and animal models of allergy. This inflammatory reaction, which may be a link between acute and chronic asthma, is blocked by glucocorticoid pretreatment. However, the role of eosinophils in late airways obstruction and the primary site of action of glucocorticoids, i.e. locally or systemically, have not been fully determined.Objectives This study was initiated to find out the role of eosinophils and neutrophils in allergen-induced late airways obstruction in the pig. The effect of pretreatment with budesonide (BUD) given locally or systemically on cellular responses seen within 8 h after allergen challenge was also studied.Methods Twenty-five minipigs were actively sensitized with Ascaris suum antigen and challenged under anaesthesia with antigen in the lower airways. Pigs were given BUD as an aerosol (l0μg/kg) or an intravenous infusion (5μg/kg) 1 h before allergen challenge. In one group, high doses of BUD (50μg/kg) were infused twice with a 3-h interval before allergen challenge. As a positive control, one group was given the BUD vehicle as an infusion and as a negative control, one group not treated with BUD was given the irrelevant antigen ovalbumin. Eosinophils and neutrophils in lung tissue specimens were detected and levels of eosinophil peroxidase (EPO) and myeloperoxidase (MPO) in bronchoalveolar lavage (BAL) fluid were measured using specific antibodies against porcine EPO and MPO.Results The number of eosinophils in lung tissue and BAL fluid and the level of EPO in BAL fluid were significantly increased 8 h after A. suum challenge in pigs not treated with BUD. With regard to possible recruitment and activation of neutrophils the only significant finding was an increase in the number of cells in BAL fluid. The eosinophil numbers and the level of EPO in BAL fluid were shown to be decreased by all BUD treatments in all the compartments studied compared to the positive control. However, the number of eosinophils in lung tissue and EPO levels in BAL fluid did not correlate with the magnitude of the late airways obstruction.Conclusion Although eosinophils are present in the bronchial wall and lumen and are apparently activated, a causative relationship between this granulocyte and the late bronchial obstruction could not be established in this model.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1996.tb00546.x
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  • 6
    Electronic Resource
    Electronic Resource
    The tryptase inhibitor APC-366 reduces the acute airway response to allergen in pigs sensitized to Ascaris suum (2002)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 32 (2002), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Tryptase is a mast cell serine protease that is released during mast cell degranulation. It has been implicated as an important enzyme in the pathophysiology of asthma, but its role in this disease is not fully elucidated.Objective In this study, we investigated the effects of a tryptase inhibitor, APC-366, on the acute allergic airway reaction in specific pathogen-free pigs sensitized to the antigen Ascaris suum.Methods APC-366 (5 mg in 1 mL of water, each dose) was given as an aerosol to seven pigs two times (t); at t = − 60 min and t = − 15 min Control pigs received water. Ascaris antigen (in 2 mL saline) was nebulized to the airways over approximately 5 min at t = 0. All aerosols were generated with an ultrasonic nebulizer.Results The allergen challenge caused an acute reaction with a significant increase in airway resistance (Raw) in the control pigs from 3.3 ± 0.6 cmH20/l/s to 10.2 ± 2.3 cmH20/l/s, while in the APC-366-treated pigs, the Raw increased from 2.6 ± 0.4 cmH20/l/s to 4.5 ± 0.7 cmH20/l/s (P 〈 0.05 compared to controls). The dynamic lung compliance (Cdyn) decreased significantly in the control pigs, but not in the APC-366-treated animals. The histamine concentration in urine in the control pigs was elevated immediately after allergen challenge, while this release was markedly reduced in the APC-366-treated pigs.Conclusion The tryptase inhibitor APC-366 reduces the acute airway response to allergen significantly. There is also a reduced elevation in urine histamine concentration after challenge in the treated pigs, compared to controls. These results indicate that inhibition of mast cell tryptase might be a useful anti-allergic treatment in asthma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2222.2002.01239.x
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  • 7
    Electronic Resource
    Electronic Resource
    Selective protective effects of nitric oxide inhalation on allergen-induced acute airway reactions in the pig (2001)
    Oxford, UK : Blackwell Science, Ltd
    Clinical & experimental allergy 31 (2001), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Nitric oxide (NO) is thought to be an important mediator of inflammatory processes during allergic reactions in the respiratory tract.Objective This study was undertaken to investigate the effects of inhalation of NO on the allergen-induced acute airway reactions in the pig.Methods Specific pathogen-free pigs were sensitized with Ascaris suum antigen and challenged with an allergen aerosol during mechanical ventilation and anaesthesia. One group (n = 8) was treated with inhaled NO (20 ppm) which was given from 30 min before allergen challenge until the experiments were completed at 120 min after challenge. A control group (n = 8) did not receive NO (〈 0.001 ppm).Results Inhalation of 20 ppm NO prevented the fall in arterial pO2/FiO2 levels that was observed in the control group (areas under the curve between 0 and 120 min were 3.7 ± 1.4 kPa/min in NO-treated pigs vs. 15.9 ± 3.4 in controls, P 〈 0.01, Mann–Whitney U-test) and it decreased baseline pulmonary arterial pressure (change from time-point − 30–0 was 3.1 ± 5.3% in the control and − 19.9 ± 3.5% in the NO group, P 〈 0.01), which in turn resulted in a lower pulmonary arterial pressure during allergen challenge. NO also caused vasodilatation in the bronchial circulation, resulting in increased bronchial vascular conductance throughout the experiment. NO inhalation caused a small, but non-significant, reduction in the allergen-induced bronchoconstrictor response, whereas histamine release, as detected in urine, was not changed. Total protein levels in bronchoalveolar lavage (BAL) fluid were significantly decreased in the NO group at 120 min after challenge compared with 45 min (373 ± 101 µg/mL vs. 631 ± 184, respectively, P 〈 0.05, Wilcoxon matched pairs test), whereas levels in the control group did not change between these two time-points (513 ± 282 vs. 599 ± 354, not significant).Conclusion These findings indicate that NO inhalation improves ventilation/perfusion matching and causes some bronchodilatation during the allergen-induced acute airway reaction, whereas histamine release is not affected. Moreover, NO inhalation enhanced the clearance of extravasated protein in the airways, possibly through increased bronchial blood flow. Even though some protective effects were seen, this study does not support a therapeutic role for exogenous NO in acute allergic reactions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2222.2001.01227.x
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  • 8
    Electronic Resource
    Electronic Resource
    Exhaled nitric oxide in a population-based study of asthma and allergy in schoolchildren (2005)
    Oxford, UK : Munksgaard International Publishers
    Allergy 60 (2005), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Exhaled nitric oxide (NO) reflects inflammation in the lower airways and is well adapted for use in children. The aims of this study were to investigate the distribution of the fraction of expired NO (FENO) in school children and to compare FENO and spirometry in relation to the International Study of Asthma and Allergies in Childhood questionnaire. The study was performed in 959 randomly selected 13–14-year-old school children in Uppsala, Sweden. Exhaled NO was measured at an inhalation rate of 0.1 l/s (FENO0.1) and a spirometric test was performed and data from these measurements were related to questionnaire data. Exhaled NO was measured according to American Thoracic Society recommendations, except the use of a mouth wash and an exhalation flow rate of 0.1 l/s. The distribution of the mean FENO0.1 values was skewed, with a preponderance of very low levels and a widespread tail of values ranging up to 102 parts per billion (ppb). Boys exhibited significantly higher mean FENO0.1 values than girls, 5.2 (4.7–5.7) vs 4.4 (4.0–4.8) ppb (geometric mean and 95% CI), P 〈 0.01). Children who reported wheezing in the last year had higher FENO0.1 values than children that had not, 8.5 (7.1–10.2) vs 4.3 (4.0–4.6) ppb, P 〈 0.001). The same association was found to most symptoms indicating hay fever and eczema. In contrast to this, only weak or inconsistent associations were found between asthma and spirometric indices. Exhaled NO levels were found to be independently related to male gender, wheeze and rhinoconjuctivitis but not to current eczema. In conclusion, exhaled NO was closely associated with reported asthma and allergy symptoms whereas spirometric indices such as percent predicted forced expiratory volume in 1 s were not. As most asthma cases in a population are mild, the findings suggest that exhaled NO is a sensitive marker of asthma and allergy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.2005.00735.x
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  • 9
    Electronic Resource
    Electronic Resource
    Characterization of airway nitric oxide in allergic rhinitis: The effect of intranasal administration of l-NAME (2003)
    Oxford, UK : Munksgaard International Publishers
    Allergy 58 (2003), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Several studies have attempted to assess nasal nitric oxide (NO) levels in allergic rhinitis (AR). However, there seem to be differences in the results obtained. We therefore wanted to investigate this further by studying airway NO in AR and controls at several modalities, and also the effect of intranasal administration of the nitric oxide synthase (NOS) inhibitorNG-nitro-l-arginine-methyl ester·HCl (l-NAME).Methods:  Airway NO was determined through repeated measurements at three flow rates of air (0.5, 3, and 9 l/min), using a single-breath method and a method of nasal aspiration, in 18 patients with birch pollen AR during season and in 18 controls.Results:  Patients with AR were characterized by no difference in nasal but higher orally exhaled NO and a larger interindividual spread in nasal and orally exhaled NO compared to controls. We also found a greater reduction in nasal NO after l-NAME in patients compared to controls.Discussion:  These results indicate that several factors determine the levels of nasal NO in rhinitis. NO production in the nasal mucosa of patients with AR may be upregulated. On the other hand, this increase could be counteracted by swelling of the mucosa and secretions resulting in impaired NO diffusion from, for example, the paranasal sinuses, where particularly high levels of NO have been found. Also, the high background levels of NO from constitutive sources in the nose may blunt smaller increases in mucosal NO output.Conclusion:  It seems that the methods for measurement of nasal NO need to be improved and standardized before we can consider to use this test in monitoring inflammation in AR.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1398-9995.2003.00098.x
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  • 10
    Electronic Resource
    Electronic Resource
    Antigen-Specific Down-Regulation of Bronchial Reactivity in Rats Sensitized Daily without Adjuvant (1986)
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 41 (1986), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Daily sensitization with ovalbumin (OA) and dog serum albumin (DSA) without adjuvant was performed in rats for 2-week periods. When the antigen was administered subcutaneously (s.c.), antibody responses were induced, as assessed in serum and bronchial lavage, and strong increases in transpulmonary pressure (TPP) after intravenous (i.v.) challenge with antigen. Sensitization without adjuvant with antigen as aerosol for similar periods also evoked pronounced antibody formation, although only weak increases of TPP were seen after challenge. Animals sensitized s.c. with OA and simultaneously exposed to OA as aerosol exhibited suppression of the TPP increase after challenge, whereas the antibody responses were not affected to any great extent. In contrast, the increase of TPP after challenge in animals similarly sensitized s.c. with DSA were not suppressed by OA given simultaneously as aerosol or vice versa.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.1986.tb00310.x
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