Effects of dexamethasone on airway hyper‐responsiveness to the adenosine A1 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, baseline a...

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Veröffentlicht in:British journal of pharmacology 1999-03, Vol.126 (6), p.1513-1521
Hauptverfasser: El‐Hashim, Ahmed Z, Banner, Katharine H, Paul, William, Page, Clive P
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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
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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&lt;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&lt;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. 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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&lt;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&lt;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. 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Drug treatments</subject><subject>Phytohemagglutinins - pharmacology</subject><subject>Purinergic P1 Receptor Agonists</subject><subject>Rabbits</subject><subject>Respiratory system</subject><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkU9rFDEYh4NY7Fq9epQcvM6aP5Nk5iLUUq1QqAc9hyTzzm6WbDIkY-vc_AiC39BPYqRru8ILObzP7-ElP4ReUbKmhHdvy25td9OaKMJaIZ6gFW2VbATv6FO0IoSohtKuO0XPS9kRUpdKPEOnlDCqRKtW6NflOIKbC04jHuC72cO8NSVFwCli4_OdWfB2mSD__vEzQ5lSLP4WIpSC54TnLWAzQEzF18Q5xRkcTHPK2GxS9GXGbnEh1ewEcV7CEeyrvk4IkDfe4Wys9TPepwHCC3QymlDg5eE9Q18_XH65uGqubz5-uji_bibWk75RppfEWDdIBjDSbrCkl-3gODfAJBv5aLkFxpgVrAWiWjADB2uFJIQr6fgZenfvnb7ZPQyunphN0FP2e5MXnYzX_2-i3-pNutVUSNEzXgWvjwUPyX_fW4E3B8AUZ8KYTXS-PHKqcm1XMX6P3fkAy5FG_-1Yl52uHetDx_r95ytKZM__AAi2oV4</recordid><startdate>199903</startdate><enddate>199903</enddate><creator>El‐Hashim, Ahmed Z</creator><creator>Banner, Katharine H</creator><creator>Paul, William</creator><creator>Page, Clive P</creator><general>Blackwell Publishing Ltd</general><general>Nature Publishing</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>5PM</scope></search><sort><creationdate>199903</creationdate><title>Effects of dexamethasone on airway hyper‐responsiveness to the adenosine A1 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-p2909-7a960abcd62eef18db0964dc33ae262f3fb3be222b524e074ead3ebb5600376c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Adenosine - analogs &amp; derivatives</topic><topic>Adenosine - pharmacology</topic><topic>adenosine A1 receptor</topic><topic>allergic inflammation</topic><topic>Animals</topic><topic>Baseline airway hyper‐responsiveness</topic><topic>Biological and medical sciences</topic><topic>Bronchial Hyperreactivity - chemically induced</topic><topic>Bronchial Hyperreactivity - prevention &amp; control</topic><topic>Bronchoalveolar Lavage Fluid - cytology</topic><topic>Cell Count - drug effects</topic><topic>Cell Division - drug effects</topic><topic>Dexamethasone - blood</topic><topic>Dexamethasone - pharmacology</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Glucocorticoids - pharmacology</topic><topic>glucocorticosteroid</topic><topic>Hypersensitivity - prevention &amp; control</topic><topic>Leukocytes, Mononuclear - cytology</topic><topic>Leukocytes, Mononuclear - drug effects</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Phytohemagglutinins - pharmacology</topic><topic>Purinergic P1 Receptor Agonists</topic><topic>Rabbits</topic><topic>Respiratory system</topic><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>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>PubMed Central (Full Participant titles)</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 A1 receptor agonist cyclo‐pentyl adenosine in an allergic rabbit model</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>1999-03</date><risdate>1999</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><coden>BJPCBM</coden><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&lt;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&lt;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><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>10217547</pmid><doi>10.1038/sj.bjp.0702455</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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subjects Adenosine - analogs & derivatives
Adenosine - pharmacology
adenosine A1 receptor
allergic inflammation
Animals
Baseline airway hyper‐responsiveness
Biological and medical sciences
Bronchial Hyperreactivity - chemically induced
Bronchial Hyperreactivity - prevention & control
Bronchoalveolar Lavage Fluid - cytology
Cell Count - drug effects
Cell Division - drug effects
Dexamethasone - blood
Dexamethasone - pharmacology
Disease Models, Animal
Female
Glucocorticoids - pharmacology
glucocorticosteroid
Hypersensitivity - prevention & control
Leukocytes, Mononuclear - cytology
Leukocytes, Mononuclear - drug effects
Male
Medical sciences
Pharmacology. Drug treatments
Phytohemagglutinins - pharmacology
Purinergic P1 Receptor Agonists
Rabbits
Respiratory system
title Effects of dexamethasone on airway hyper‐responsiveness to the adenosine A1 receptor agonist cyclo‐pentyl adenosine in an allergic rabbit model
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