In vivo and in vitro effects of glucocorticosteroids on arachidonic acid metabolism and monocyte function in nonasthmatic humans
Glucocorticosteroids are used as anti-inflammatory agents in a range of diseases, however, their mechanism of action is unknown. Recently, inhibition of arachidonic acid metabolism has been suggested as one possible mechanism of action. A series of experiments were undertaken in nonasthmatic humans...
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Veröffentlicht in: | The European respiratory journal 1992-06, Vol.5 (6), p.712-716 |
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description | Glucocorticosteroids are used as anti-inflammatory agents in a range of diseases, however, their mechanism of action is unknown. Recently, inhibition of arachidonic acid metabolism has been suggested as one possible mechanism of action. A series of experiments were undertaken in nonasthmatic humans to examine the effects of oral prednisolone and dexamethasone and inhaled budesonide on the excretion of the urinary leukotriene E4 (LTE4), an established marker of total body leukotriene generation in vivo. In addition, the effect of the drugs on the in vitro and ex-vivo function of monocytes was examined. In vitro dexamethasone greater than 10(-8) M inhibited the thromboxane A2 (TxA2) release from human monocytes, an effect which recovered within 24 h. In vivo, neither inhaled budesonide (1.6 mg.day-1 for 7 days), nor a standard therapeutic dose of oral prednisolone (30 mg.day-1 for 3 days), nor high doses of oral dexamethasone (8 mg.day-1 for 2 days) altered the excretion of urinary LTE4, despite the latter completely suppressing endogenous cortisol production. The ex-vivo zymosan stimulated release of TxA2 release from monocytes was not altered by the standard dose prednisolone, but was reduced by high dose dexamethasone and inhaled budesonide. This study shows that high doses of systemic steroids have little effect on arachidonic acid metabolism in normal nonasthmatic humans. Inhaled budesonide, however, does reduce arachidonic acid metabolism in circulating monocytes, presumably by affecting these cells during their passage through the lung. |
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Recently, inhibition of arachidonic acid metabolism has been suggested as one possible mechanism of action. A series of experiments were undertaken in nonasthmatic humans to examine the effects of oral prednisolone and dexamethasone and inhaled budesonide on the excretion of the urinary leukotriene E4 (LTE4), an established marker of total body leukotriene generation in vivo. In addition, the effect of the drugs on the in vitro and ex-vivo function of monocytes was examined. In vitro dexamethasone greater than 10(-8) M inhibited the thromboxane A2 (TxA2) release from human monocytes, an effect which recovered within 24 h. In vivo, neither inhaled budesonide (1.6 mg.day-1 for 7 days), nor a standard therapeutic dose of oral prednisolone (30 mg.day-1 for 3 days), nor high doses of oral dexamethasone (8 mg.day-1 for 2 days) altered the excretion of urinary LTE4, despite the latter completely suppressing endogenous cortisol production. The ex-vivo zymosan stimulated release of TxA2 release from monocytes was not altered by the standard dose prednisolone, but was reduced by high dose dexamethasone and inhaled budesonide. This study shows that high doses of systemic steroids have little effect on arachidonic acid metabolism in normal nonasthmatic humans. Inhaled budesonide, however, does reduce arachidonic acid metabolism in circulating monocytes, presumably by affecting these cells during their passage through the lung.</description><identifier>ISSN: 0903-1936</identifier><identifier>EISSN: 1399-3003</identifier><identifier>DOI: 10.1183/09031936.93.05060712</identifier><identifier>PMID: 1321056</identifier><language>eng</language><publisher>Leeds: Eur Respiratory Soc</publisher><subject>Administration, Topical ; Adult ; Aerosols ; Anti-Inflammatory Agents - pharmacology ; Arachidonic Acid - metabolism ; Biological and medical sciences ; Bones, joints and connective tissue. Antiinflammatory agents ; Budesonide ; Dexamethasone - pharmacology ; Double-Blind Method ; Drug Evaluation ; Female ; Glucocorticoids ; Humans ; In Vitro Techniques ; Leukotriene E4 ; Male ; Medical sciences ; Monocytes - drug effects ; Pharmacology. 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Recently, inhibition of arachidonic acid metabolism has been suggested as one possible mechanism of action. A series of experiments were undertaken in nonasthmatic humans to examine the effects of oral prednisolone and dexamethasone and inhaled budesonide on the excretion of the urinary leukotriene E4 (LTE4), an established marker of total body leukotriene generation in vivo. In addition, the effect of the drugs on the in vitro and ex-vivo function of monocytes was examined. In vitro dexamethasone greater than 10(-8) M inhibited the thromboxane A2 (TxA2) release from human monocytes, an effect which recovered within 24 h. In vivo, neither inhaled budesonide (1.6 mg.day-1 for 7 days), nor a standard therapeutic dose of oral prednisolone (30 mg.day-1 for 3 days), nor high doses of oral dexamethasone (8 mg.day-1 for 2 days) altered the excretion of urinary LTE4, despite the latter completely suppressing endogenous cortisol production. The ex-vivo zymosan stimulated release of TxA2 release from monocytes was not altered by the standard dose prednisolone, but was reduced by high dose dexamethasone and inhaled budesonide. This study shows that high doses of systemic steroids have little effect on arachidonic acid metabolism in normal nonasthmatic humans. Inhaled budesonide, however, does reduce arachidonic acid metabolism in circulating monocytes, presumably by affecting these cells during their passage through the lung.</description><subject>Administration, Topical</subject><subject>Adult</subject><subject>Aerosols</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Arachidonic Acid - metabolism</subject><subject>Biological and medical sciences</subject><subject>Bones, joints and connective tissue. Antiinflammatory agents</subject><subject>Budesonide</subject><subject>Dexamethasone - pharmacology</subject><subject>Double-Blind Method</subject><subject>Drug Evaluation</subject><subject>Female</subject><subject>Glucocorticoids</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Leukotriene E4</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Monocytes - drug effects</subject><subject>Pharmacology. Drug treatments</subject><subject>Prednisolone - pharmacology</subject><subject>Pregnenediones - pharmacology</subject><subject>SRS-A - analogs & derivatives</subject><subject>SRS-A - urine</subject><subject>Thromboxanes - metabolism</subject><issn>0903-1936</issn><issn>1399-3003</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkM1u1TAQRi0EKrc_bwCSF4hdLrYncZIlqgpUqsSGrq3JxGlcJXaxk6LueHSc3kth5ZHnfMfWx9g7KfZSNvBJtAJkC3rfwl5UQotaqldsJ6FtCxACXrPdhhQb85adpnQvhNQlyBN2IkFJUekd-33t-aN7DBx9z902LzFwOwyWlsTDwO-mlQKFuDgKabExuD7fe44RaXR98I44kuv5bBfswuTS_Oyagw_0tFg-rJ4WlxPZ7oPHtIwzZhsf1xl9OmdvBpySvTieZ-z2y9WPy2_Fzfev15efbwrKX1UFyXJoFGqorKrJdr3VLSgEBVDWnSVNvdBljUPdNFZCg4JQyJ4IukrVbQ1n7OPB-xDDz9WmxcwukZ0m9DasydQg6lKrKoPlAaQYUop2MA_RzRifjBRmK978Ld60eT4Wn2Pvj_61m23_L3RoOu8_HPeYCKchoieXXrAKGqXgP2x0d-MvF61JM05Tlkpj431ltNle-wNQxZms</recordid><startdate>199206</startdate><enddate>199206</enddate><creator>Manso, G</creator><creator>Baker, AJ</creator><creator>Taylor, IK</creator><creator>Fuller, RW</creator><general>Eur Respiratory Soc</general><general>Maney</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>199206</creationdate><title>In vivo and in vitro effects of glucocorticosteroids on arachidonic acid metabolism and monocyte function in nonasthmatic humans</title><author>Manso, G ; Baker, AJ ; Taylor, IK ; Fuller, RW</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3212-c14f82a635e27cebde6932a323347bec6cd0647af788e138a0ca01dcc3b527973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1992</creationdate><topic>Administration, Topical</topic><topic>Adult</topic><topic>Aerosols</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Arachidonic Acid - metabolism</topic><topic>Biological and medical sciences</topic><topic>Bones, joints and connective tissue. Antiinflammatory agents</topic><topic>Budesonide</topic><topic>Dexamethasone - pharmacology</topic><topic>Double-Blind Method</topic><topic>Drug Evaluation</topic><topic>Female</topic><topic>Glucocorticoids</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Leukotriene E4</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Monocytes - drug effects</topic><topic>Pharmacology. Drug treatments</topic><topic>Prednisolone - pharmacology</topic><topic>Pregnenediones - pharmacology</topic><topic>SRS-A - analogs & derivatives</topic><topic>SRS-A - urine</topic><topic>Thromboxanes - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Manso, G</creatorcontrib><creatorcontrib>Baker, AJ</creatorcontrib><creatorcontrib>Taylor, IK</creatorcontrib><creatorcontrib>Fuller, RW</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>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The European respiratory journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Manso, G</au><au>Baker, AJ</au><au>Taylor, IK</au><au>Fuller, RW</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vivo and in vitro effects of glucocorticosteroids on arachidonic acid metabolism and monocyte function in nonasthmatic humans</atitle><jtitle>The European respiratory journal</jtitle><addtitle>Eur Respir J</addtitle><date>1992-06</date><risdate>1992</risdate><volume>5</volume><issue>6</issue><spage>712</spage><epage>716</epage><pages>712-716</pages><issn>0903-1936</issn><eissn>1399-3003</eissn><abstract>Glucocorticosteroids are used as anti-inflammatory agents in a range of diseases, however, their mechanism of action is unknown. Recently, inhibition of arachidonic acid metabolism has been suggested as one possible mechanism of action. A series of experiments were undertaken in nonasthmatic humans to examine the effects of oral prednisolone and dexamethasone and inhaled budesonide on the excretion of the urinary leukotriene E4 (LTE4), an established marker of total body leukotriene generation in vivo. In addition, the effect of the drugs on the in vitro and ex-vivo function of monocytes was examined. In vitro dexamethasone greater than 10(-8) M inhibited the thromboxane A2 (TxA2) release from human monocytes, an effect which recovered within 24 h. In vivo, neither inhaled budesonide (1.6 mg.day-1 for 7 days), nor a standard therapeutic dose of oral prednisolone (30 mg.day-1 for 3 days), nor high doses of oral dexamethasone (8 mg.day-1 for 2 days) altered the excretion of urinary LTE4, despite the latter completely suppressing endogenous cortisol production. The ex-vivo zymosan stimulated release of TxA2 release from monocytes was not altered by the standard dose prednisolone, but was reduced by high dose dexamethasone and inhaled budesonide. This study shows that high doses of systemic steroids have little effect on arachidonic acid metabolism in normal nonasthmatic humans. Inhaled budesonide, however, does reduce arachidonic acid metabolism in circulating monocytes, presumably by affecting these cells during their passage through the lung.</abstract><cop>Leeds</cop><pub>Eur Respiratory Soc</pub><pmid>1321056</pmid><doi>10.1183/09031936.93.05060712</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Administration, Topical Adult Aerosols Anti-Inflammatory Agents - pharmacology Arachidonic Acid - metabolism Biological and medical sciences Bones, joints and connective tissue. Antiinflammatory agents Budesonide Dexamethasone - pharmacology Double-Blind Method Drug Evaluation Female Glucocorticoids Humans In Vitro Techniques Leukotriene E4 Male Medical sciences Monocytes - drug effects Pharmacology. Drug treatments Prednisolone - pharmacology Pregnenediones - pharmacology SRS-A - analogs & derivatives SRS-A - urine Thromboxanes - metabolism |
title | In vivo and in vitro effects of glucocorticosteroids on arachidonic acid metabolism and monocyte function in nonasthmatic humans |
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