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Effects of dexamethasone on airway hyper‐responsiveness to the adenosine A 1 receptor agonist cyclo‐pentyl adenosine in an allergic rabbit model
New Zealand White (NZW) rabbits were immunized within 24 h of birth with Alternaria tenuis in aluminium hydroxide (Al (OH) 3 ) (i.p.) or sham immunized (saline plus Al (OH) 3 i.p.) and subsequently injected with the allergen (i.p.) or sham‐immunized for the next 3 months. At 3 months of age, baselin...
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Published in: | British journal of pharmacology 2009-01, Vol.126 (6), p.1513-1521 |
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container_title | British journal of pharmacology |
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creator | El‐Hashim, Ahmed Z Banner, Katharine H Paul, William Page, Clive P |
description | New Zealand White (NZW) rabbits were immunized within 24 h of birth with
Alternaria tenuis
in aluminium hydroxide (Al (OH)
3
) (i.p.) or sham immunized (saline plus Al (OH)
3
i.p.) and subsequently injected with the allergen (i.p.) or sham‐immunized for the next 3 months. At 3 months of age, baseline airway responsiveness was assessed using cyclo‐pentyl adenosine (CPA). Bronchoalveolar lavage (BAL) was performed in all animals and samples of peripheral blood were collected from some animals for estimation of dexamethasone levels. In some animals, blood was collected at the end of the experiment and cellular function was assessed by measurement of
ex vivo
proliferation of mononuclear cells in response to phytohaemagglutinin (PHA).
Allergen immunization significantly increased baseline airway responsiveness to inhaled CPA (
P |
doi_str_mv | 10.1038/sj.bjp.0702455 |
format | article |
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Alternaria tenuis
in aluminium hydroxide (Al (OH)
3
) (i.p.) or sham immunized (saline plus Al (OH)
3
i.p.) and subsequently injected with the allergen (i.p.) or sham‐immunized for the next 3 months. At 3 months of age, baseline airway responsiveness was assessed using cyclo‐pentyl adenosine (CPA). Bronchoalveolar lavage (BAL) was performed in all animals and samples of peripheral blood were collected from some animals for estimation of dexamethasone levels. In some animals, blood was collected at the end of the experiment and cellular function was assessed by measurement of
ex vivo
proliferation of mononuclear cells in response to phytohaemagglutinin (PHA).
Allergen immunization significantly increased baseline airway responsiveness to inhaled CPA (
P
<0.05) in comparison with sham‐immunized animals, at 3 months after immunization. Dexamethasone (0.5 mg kg
−1
day
−1
) treatment for 1 month did not modify this established airway hyper‐responsiveness to CPA. Dexamethasone treatment did not affect either total or differential cell numbers in BAL fluid during the 4 week period, although significant plasma levels of dexamethasone were achieved in dexamethasone treated animals.
Treatment of rabbits with dexamethasone (0.1 mg kg
−1
i.p.), 6 h prior to each allergen injection from the neonatal stage, significantly reduced baseline airway hyper‐responsiveness to CPA measured at 3 months (
P
<0.05). There was no significant difference in either total or differential cell numbers in BAL fluid, or any difference in mitogen‐induced proliferation of mononuclear cells between dexamethasone and vehicle treated rabbits.
These results suggest that introduction of glucocorticosteroids in early life can prevent baseline airway hyper‐responsiveness to inhaled CPA in allergic rabbits. However, once established, such underlying airway hyper‐responsiveness is difficult to resolve, even with prolonged treatment with glucocorticosteroids.
British Journal of Pharmacology
(1999)
126
, 1513–1521; doi:
10.1038/sj.bjp.0702455</description><identifier>ISSN: 0007-1188</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1038/sj.bjp.0702455</identifier><language>eng</language><ispartof>British journal of pharmacology, 2009-01, Vol.126 (6), p.1513-1521</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c845-aee17fe206969f6a1c2a78502338a4028f757f4bec8fec17392cec91034cc6c93</citedby><cites>FETCH-LOGICAL-c845-aee17fe206969f6a1c2a78502338a4028f757f4bec8fec17392cec91034cc6c93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>El‐Hashim, Ahmed Z</creatorcontrib><creatorcontrib>Banner, Katharine H</creatorcontrib><creatorcontrib>Paul, William</creatorcontrib><creatorcontrib>Page, Clive P</creatorcontrib><title>Effects of dexamethasone on airway hyper‐responsiveness to the adenosine A 1 receptor agonist cyclo‐pentyl adenosine in an allergic rabbit model</title><title>British journal of pharmacology</title><description>New Zealand White (NZW) rabbits were immunized within 24 h of birth with
Alternaria tenuis
in aluminium hydroxide (Al (OH)
3
) (i.p.) or sham immunized (saline plus Al (OH)
3
i.p.) and subsequently injected with the allergen (i.p.) or sham‐immunized for the next 3 months. At 3 months of age, baseline airway responsiveness was assessed using cyclo‐pentyl adenosine (CPA). Bronchoalveolar lavage (BAL) was performed in all animals and samples of peripheral blood were collected from some animals for estimation of dexamethasone levels. In some animals, blood was collected at the end of the experiment and cellular function was assessed by measurement of
ex vivo
proliferation of mononuclear cells in response to phytohaemagglutinin (PHA).
Allergen immunization significantly increased baseline airway responsiveness to inhaled CPA (
P
<0.05) in comparison with sham‐immunized animals, at 3 months after immunization. Dexamethasone (0.5 mg kg
−1
day
−1
) treatment for 1 month did not modify this established airway hyper‐responsiveness to CPA. Dexamethasone treatment did not affect either total or differential cell numbers in BAL fluid during the 4 week period, although significant plasma levels of dexamethasone were achieved in dexamethasone treated animals.
Treatment of rabbits with dexamethasone (0.1 mg kg
−1
i.p.), 6 h prior to each allergen injection from the neonatal stage, significantly reduced baseline airway hyper‐responsiveness to CPA measured at 3 months (
P
<0.05). There was no significant difference in either total or differential cell numbers in BAL fluid, or any difference in mitogen‐induced proliferation of mononuclear cells between dexamethasone and vehicle treated rabbits.
These results suggest that introduction of glucocorticosteroids in early life can prevent baseline airway hyper‐responsiveness to inhaled CPA in allergic rabbits. However, once established, such underlying airway hyper‐responsiveness is difficult to resolve, even with prolonged treatment with glucocorticosteroids.
British Journal of Pharmacology
(1999)
126
, 1513–1521; doi:
10.1038/sj.bjp.0702455</description><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><recordid>eNpNkM1KxDAUhYMoOI5uXecFWpO2adLlMIw_ILiZfUkzNzMpnabkBrU7H8GFT-iTGHEWwoWzuOccOB8ht5zlnJXqDvu866ecSVZUQpyRBa9knYlS8XOyYIzJjHOlLskVYs9YekqxIF8ba8FEpN7SHbzrI8SDRj8C9SPVLrzpmR7mCcL3x2cAnPyI7hVGQKTR03gAqncwenQpsaKcBjAwRR-o3vvRYaRmNoNP4QnGOA__3C71pxsGCHtnaNBd5yI9-h0M1-TC6gHh5qRLsr3fbNeP2fPLw9N69ZwZVYlMA3BpoWB1Uze21twUWirBirJUumKFslJIW3VgVJrIZdkUBkyTWFXG1KYplyT_qzXBIwaw7RTcUYe55az9Rdpi3yak7Qlp-QNVRXCL</recordid><startdate>20090129</startdate><enddate>20090129</enddate><creator>El‐Hashim, Ahmed Z</creator><creator>Banner, Katharine H</creator><creator>Paul, William</creator><creator>Page, Clive P</creator><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20090129</creationdate><title>Effects of dexamethasone on airway hyper‐responsiveness to the adenosine A 1 receptor agonist cyclo‐pentyl adenosine in an allergic rabbit model</title><author>El‐Hashim, Ahmed Z ; Banner, Katharine H ; Paul, William ; Page, Clive P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c845-aee17fe206969f6a1c2a78502338a4028f757f4bec8fec17392cec91034cc6c93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>El‐Hashim, Ahmed Z</creatorcontrib><creatorcontrib>Banner, Katharine H</creatorcontrib><creatorcontrib>Paul, William</creatorcontrib><creatorcontrib>Page, Clive P</creatorcontrib><collection>CrossRef</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>El‐Hashim, Ahmed Z</au><au>Banner, Katharine H</au><au>Paul, William</au><au>Page, Clive P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of dexamethasone on airway hyper‐responsiveness to the adenosine A 1 receptor agonist cyclo‐pentyl adenosine in an allergic rabbit model</atitle><jtitle>British journal of pharmacology</jtitle><date>2009-01-29</date><risdate>2009</risdate><volume>126</volume><issue>6</issue><spage>1513</spage><epage>1521</epage><pages>1513-1521</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><abstract>New Zealand White (NZW) rabbits were immunized within 24 h of birth with
Alternaria tenuis
in aluminium hydroxide (Al (OH)
3
) (i.p.) or sham immunized (saline plus Al (OH)
3
i.p.) and subsequently injected with the allergen (i.p.) or sham‐immunized for the next 3 months. At 3 months of age, baseline airway responsiveness was assessed using cyclo‐pentyl adenosine (CPA). Bronchoalveolar lavage (BAL) was performed in all animals and samples of peripheral blood were collected from some animals for estimation of dexamethasone levels. In some animals, blood was collected at the end of the experiment and cellular function was assessed by measurement of
ex vivo
proliferation of mononuclear cells in response to phytohaemagglutinin (PHA).
Allergen immunization significantly increased baseline airway responsiveness to inhaled CPA (
P
<0.05) in comparison with sham‐immunized animals, at 3 months after immunization. Dexamethasone (0.5 mg kg
−1
day
−1
) treatment for 1 month did not modify this established airway hyper‐responsiveness to CPA. Dexamethasone treatment did not affect either total or differential cell numbers in BAL fluid during the 4 week period, although significant plasma levels of dexamethasone were achieved in dexamethasone treated animals.
Treatment of rabbits with dexamethasone (0.1 mg kg
−1
i.p.), 6 h prior to each allergen injection from the neonatal stage, significantly reduced baseline airway hyper‐responsiveness to CPA measured at 3 months (
P
<0.05). There was no significant difference in either total or differential cell numbers in BAL fluid, or any difference in mitogen‐induced proliferation of mononuclear cells between dexamethasone and vehicle treated rabbits.
These results suggest that introduction of glucocorticosteroids in early life can prevent baseline airway hyper‐responsiveness to inhaled CPA in allergic rabbits. However, once established, such underlying airway hyper‐responsiveness is difficult to resolve, even with prolonged treatment with glucocorticosteroids.
British Journal of Pharmacology
(1999)
126
, 1513–1521; doi:
10.1038/sj.bjp.0702455</abstract><doi>10.1038/sj.bjp.0702455</doi><tpages>9</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0007-1188 |
ispartof | British journal of pharmacology, 2009-01, Vol.126 (6), p.1513-1521 |
issn | 0007-1188 1476-5381 |
language | eng |
recordid | cdi_crossref_primary_10_1038_sj_bjp_0702455 |
source | Wiley; PMC (PubMed Central) |
title | Effects of dexamethasone on airway hyper‐responsiveness to the adenosine A 1 receptor agonist cyclo‐pentyl adenosine in an allergic rabbit model |
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