Clinical, Cellular, and Molecular Effects of Corticosteroids on the Response to Intradermal Lipopolysaccharide Administration in Healthy Volunteers
The intradermal lipopolysaccharide (LPS) challenge in healthy volunteers has proven to be a valuable tool to study local inflammation in vivo. In the current study the inhibitory effects of oral and topical corticosteroid treatment on intradermal LPS responses were evaluated to benchmark the challen...
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| Veröffentlicht in: | Clinical pharmacology and therapeutics 2022-04, Vol.111 (4), p.964-971 |
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| creator | Buters, Thomas P. Hameeteman, Pieter W. Jansen, Iris M.E. Hindevoort, Floris C. ten Voorde, Wouter Grievink, Hendrika W. Schoonakker, Mascha Kam, Marieke L. Gilroy, Derek W. Feiss, Gary Rissmann, Robert Jansen, Manon A.A. Burggraaf, Jacobus Moerland, Matthijs |
| description | The intradermal lipopolysaccharide (LPS) challenge in healthy volunteers has proven to be a valuable tool to study local inflammation in vivo. In the current study the inhibitory effects of oral and topical corticosteroid treatment on intradermal LPS responses were evaluated to benchmark the challenge for future investigational drugs. Twenty‐four healthy male volunteers received a two‐and‐a‐half‐day twice daily (b.i.d.) pretreatment with topical clobetasol propionate 0.05% and six healthy volunteers received a two‐and‐a‐half‐day b.i.d. pretreatment with oral prednisolone at 0.25 mg/kg body weight per administration. Participants received one injection regimen of either 0, 2, or 4 intradermal LPS injections (5 ng LPS in 50 µL 0.9% sodium chloride solution). The LPS response was evaluated by noninvasive (perfusion, skin temperature, and erythema) and invasive assessments (cellular and cytokine responses) in suction blister exudate. Both corticosteroids significantly suppressed the clinical inflammatory response (erythema P = 0.0001 for clobetasol and P = 0.0016 for prednisolone; heat P = 0.0245 for clobetasol, perfusion P |
| doi_str_mv | 10.1002/cpt.2516 |
| format | Article |
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In the current study the inhibitory effects of oral and topical corticosteroid treatment on intradermal LPS responses were evaluated to benchmark the challenge for future investigational drugs. Twenty‐four healthy male volunteers received a two‐and‐a‐half‐day twice daily (b.i.d.) pretreatment with topical clobetasol propionate 0.05% and six healthy volunteers received a two‐and‐a‐half‐day b.i.d. pretreatment with oral prednisolone at 0.25 mg/kg body weight per administration. Participants received one injection regimen of either 0, 2, or 4 intradermal LPS injections (5 ng LPS in 50 µL 0.9% sodium chloride solution). The LPS response was evaluated by noninvasive (perfusion, skin temperature, and erythema) and invasive assessments (cellular and cytokine responses) in suction blister exudate. Both corticosteroids significantly suppressed the clinical inflammatory response (erythema P = 0.0001 for clobetasol and P = 0.0016 for prednisolone; heat P = 0.0245 for clobetasol, perfusion P < 0.0001 for clobetasol and P = 0.0036 for prednisolone). Clobetasol also significantly reduced the number of monocytes subsets, dendritic cells, natural killer cells, and T cells in blister exudate. A similar effect was observed for prednisolone. No relevant corticosteroid effects were observed on the cytokine response to LPS. We successfully demonstrated that the anti‐inflammatory effects of corticosteroids can be detected using our intradermal LPS challenge model, validating it for evaluation of future investigational drugs, as an initial assessment of the anti‐inflammatory effects of such compounds in a minimally invasive manner.</description><identifier>ISSN: 0009-9236</identifier><identifier>EISSN: 1532-6535</identifier><identifier>DOI: 10.1002/cpt.2516</identifier><identifier>PMID: 34935141</identifier><language>eng</language><publisher>United States: John Wiley and Sons Inc</publisher><subject>Adrenal Cortex Hormones ; Anti-Inflammatory Agents - therapeutic use ; Blister - drug therapy ; Clobetasol - pharmacology ; Clobetasol - therapeutic use ; Cytokines ; Drugs, Investigational ; Erythema - drug therapy ; Glucocorticoids - pharmacology ; Healthy Volunteers ; Humans ; Lipopolysaccharides ; Male ; Prednisolone - pharmacology</subject><ispartof>Clinical pharmacology and therapeutics, 2022-04, Vol.111 (4), p.964-971</ispartof><rights>2021 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.</rights><rights>2021 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4106-7e4a873be2e29d4c64b54f35eb1aa839f90fb2e928f41a6fe8cc8369223b163f3</citedby><cites>FETCH-LOGICAL-c4106-7e4a873be2e29d4c64b54f35eb1aa839f90fb2e928f41a6fe8cc8369223b163f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcpt.2516$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcpt.2516$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,315,781,785,886,1418,27929,27930,45579,45580</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34935141$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Buters, Thomas P.</creatorcontrib><creatorcontrib>Hameeteman, Pieter W.</creatorcontrib><creatorcontrib>Jansen, Iris M.E.</creatorcontrib><creatorcontrib>Hindevoort, Floris C.</creatorcontrib><creatorcontrib>ten Voorde, Wouter</creatorcontrib><creatorcontrib>Grievink, Hendrika W.</creatorcontrib><creatorcontrib>Schoonakker, Mascha</creatorcontrib><creatorcontrib>Kam, Marieke L.</creatorcontrib><creatorcontrib>Gilroy, Derek W.</creatorcontrib><creatorcontrib>Feiss, Gary</creatorcontrib><creatorcontrib>Rissmann, Robert</creatorcontrib><creatorcontrib>Jansen, Manon A.A.</creatorcontrib><creatorcontrib>Burggraaf, Jacobus</creatorcontrib><creatorcontrib>Moerland, Matthijs</creatorcontrib><title>Clinical, Cellular, and Molecular Effects of Corticosteroids on the Response to Intradermal Lipopolysaccharide Administration in Healthy Volunteers</title><title>Clinical pharmacology and therapeutics</title><addtitle>Clin Pharmacol Ther</addtitle><description>The intradermal lipopolysaccharide (LPS) challenge in healthy volunteers has proven to be a valuable tool to study local inflammation in vivo. In the current study the inhibitory effects of oral and topical corticosteroid treatment on intradermal LPS responses were evaluated to benchmark the challenge for future investigational drugs. Twenty‐four healthy male volunteers received a two‐and‐a‐half‐day twice daily (b.i.d.) pretreatment with topical clobetasol propionate 0.05% and six healthy volunteers received a two‐and‐a‐half‐day b.i.d. pretreatment with oral prednisolone at 0.25 mg/kg body weight per administration. Participants received one injection regimen of either 0, 2, or 4 intradermal LPS injections (5 ng LPS in 50 µL 0.9% sodium chloride solution). The LPS response was evaluated by noninvasive (perfusion, skin temperature, and erythema) and invasive assessments (cellular and cytokine responses) in suction blister exudate. Both corticosteroids significantly suppressed the clinical inflammatory response (erythema P = 0.0001 for clobetasol and P = 0.0016 for prednisolone; heat P = 0.0245 for clobetasol, perfusion P < 0.0001 for clobetasol and P = 0.0036 for prednisolone). Clobetasol also significantly reduced the number of monocytes subsets, dendritic cells, natural killer cells, and T cells in blister exudate. A similar effect was observed for prednisolone. No relevant corticosteroid effects were observed on the cytokine response to LPS. We successfully demonstrated that the anti‐inflammatory effects of corticosteroids can be detected using our intradermal LPS challenge model, validating it for evaluation of future investigational drugs, as an initial assessment of the anti‐inflammatory effects of such compounds in a minimally invasive manner.</description><subject>Adrenal Cortex Hormones</subject><subject>Anti-Inflammatory Agents - therapeutic use</subject><subject>Blister - drug therapy</subject><subject>Clobetasol - pharmacology</subject><subject>Clobetasol - therapeutic use</subject><subject>Cytokines</subject><subject>Drugs, Investigational</subject><subject>Erythema - drug therapy</subject><subject>Glucocorticoids - pharmacology</subject><subject>Healthy Volunteers</subject><subject>Humans</subject><subject>Lipopolysaccharides</subject><subject>Male</subject><subject>Prednisolone - pharmacology</subject><issn>0009-9236</issn><issn>1532-6535</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNp1kc9u1DAQhy0EoktB4gmQjxya4n_xxhekKiq00iIQKlwtxxmzRk4cbG_RPkdfuF5aChw4WeP5_M3IP4ReUnJKCWFv7FJOWUvlI7SiLWeNbHn7GK0IIapRjMsj9Czn77UUquueoiMuFG-poCt00wc_e2vCCe4hhF0w6QSbecQfYgB7KPG5c2BLxtHhPqbibcwFUvRjvZpx2QL-DHmJcwZcIr6cSzIjpMkEvPFLXGLYZ2Pt1iQ_Aj4bpzovV6b4-trP-AJMKNs9_hrDbi4AKT9HT5wJGV7cn8foy7vzq_6i2Xx8f9mfbRorKJHNGoTp1nwABkyNwkoxtMLxFgZqTMeVU8QNDBTrnKBGOuis7bhUjPGBSu74MXp75112wwSjhcPqQS_JTybtdTRe_9uZ_VZ_i9dacdIKua6C1_eCFH_sIBc9-WzrN5oZ4i5rJilbc96q7g9qU8w5gXsYQ4k-ZKhrhvqQYUVf_b3WA_g7tAo0d8BPH2D_X5HuP139Et4CfZqqGg</recordid><startdate>202204</startdate><enddate>202204</enddate><creator>Buters, Thomas P.</creator><creator>Hameeteman, Pieter W.</creator><creator>Jansen, Iris M.E.</creator><creator>Hindevoort, Floris C.</creator><creator>ten Voorde, Wouter</creator><creator>Grievink, Hendrika W.</creator><creator>Schoonakker, Mascha</creator><creator>Kam, Marieke L.</creator><creator>Gilroy, Derek W.</creator><creator>Feiss, Gary</creator><creator>Rissmann, Robert</creator><creator>Jansen, Manon A.A.</creator><creator>Burggraaf, Jacobus</creator><creator>Moerland, Matthijs</creator><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</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><scope>5PM</scope></search><sort><creationdate>202204</creationdate><title>Clinical, Cellular, and Molecular Effects of Corticosteroids on the Response to Intradermal Lipopolysaccharide Administration in Healthy Volunteers</title><author>Buters, Thomas P. ; Hameeteman, Pieter W. ; Jansen, Iris M.E. ; Hindevoort, Floris C. ; ten Voorde, Wouter ; Grievink, Hendrika W. ; Schoonakker, Mascha ; Kam, Marieke L. ; Gilroy, Derek W. ; Feiss, Gary ; Rissmann, Robert ; Jansen, Manon A.A. ; Burggraaf, Jacobus ; Moerland, Matthijs</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4106-7e4a873be2e29d4c64b54f35eb1aa839f90fb2e928f41a6fe8cc8369223b163f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adrenal Cortex Hormones</topic><topic>Anti-Inflammatory Agents - therapeutic use</topic><topic>Blister - drug therapy</topic><topic>Clobetasol - pharmacology</topic><topic>Clobetasol - therapeutic use</topic><topic>Cytokines</topic><topic>Drugs, Investigational</topic><topic>Erythema - drug therapy</topic><topic>Glucocorticoids - pharmacology</topic><topic>Healthy Volunteers</topic><topic>Humans</topic><topic>Lipopolysaccharides</topic><topic>Male</topic><topic>Prednisolone - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Buters, Thomas P.</creatorcontrib><creatorcontrib>Hameeteman, Pieter W.</creatorcontrib><creatorcontrib>Jansen, Iris M.E.</creatorcontrib><creatorcontrib>Hindevoort, Floris C.</creatorcontrib><creatorcontrib>ten Voorde, Wouter</creatorcontrib><creatorcontrib>Grievink, Hendrika W.</creatorcontrib><creatorcontrib>Schoonakker, Mascha</creatorcontrib><creatorcontrib>Kam, Marieke L.</creatorcontrib><creatorcontrib>Gilroy, Derek W.</creatorcontrib><creatorcontrib>Feiss, Gary</creatorcontrib><creatorcontrib>Rissmann, Robert</creatorcontrib><creatorcontrib>Jansen, Manon A.A.</creatorcontrib><creatorcontrib>Burggraaf, Jacobus</creatorcontrib><creatorcontrib>Moerland, Matthijs</creatorcontrib><collection>Wiley Online Library (Open Access Collection)</collection><collection>Wiley Online Library (Open Access Collection)</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical pharmacology and therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Buters, Thomas P.</au><au>Hameeteman, Pieter W.</au><au>Jansen, Iris M.E.</au><au>Hindevoort, Floris C.</au><au>ten Voorde, Wouter</au><au>Grievink, Hendrika W.</au><au>Schoonakker, Mascha</au><au>Kam, Marieke L.</au><au>Gilroy, Derek W.</au><au>Feiss, Gary</au><au>Rissmann, Robert</au><au>Jansen, Manon A.A.</au><au>Burggraaf, Jacobus</au><au>Moerland, Matthijs</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical, Cellular, and Molecular Effects of Corticosteroids on the Response to Intradermal Lipopolysaccharide Administration in Healthy Volunteers</atitle><jtitle>Clinical pharmacology and therapeutics</jtitle><addtitle>Clin Pharmacol Ther</addtitle><date>2022-04</date><risdate>2022</risdate><volume>111</volume><issue>4</issue><spage>964</spage><epage>971</epage><pages>964-971</pages><issn>0009-9236</issn><eissn>1532-6535</eissn><abstract>The intradermal lipopolysaccharide (LPS) challenge in healthy volunteers has proven to be a valuable tool to study local inflammation in vivo. In the current study the inhibitory effects of oral and topical corticosteroid treatment on intradermal LPS responses were evaluated to benchmark the challenge for future investigational drugs. Twenty‐four healthy male volunteers received a two‐and‐a‐half‐day twice daily (b.i.d.) pretreatment with topical clobetasol propionate 0.05% and six healthy volunteers received a two‐and‐a‐half‐day b.i.d. pretreatment with oral prednisolone at 0.25 mg/kg body weight per administration. Participants received one injection regimen of either 0, 2, or 4 intradermal LPS injections (5 ng LPS in 50 µL 0.9% sodium chloride solution). The LPS response was evaluated by noninvasive (perfusion, skin temperature, and erythema) and invasive assessments (cellular and cytokine responses) in suction blister exudate. Both corticosteroids significantly suppressed the clinical inflammatory response (erythema P = 0.0001 for clobetasol and P = 0.0016 for prednisolone; heat P = 0.0245 for clobetasol, perfusion P < 0.0001 for clobetasol and P = 0.0036 for prednisolone). Clobetasol also significantly reduced the number of monocytes subsets, dendritic cells, natural killer cells, and T cells in blister exudate. A similar effect was observed for prednisolone. No relevant corticosteroid effects were observed on the cytokine response to LPS. We successfully demonstrated that the anti‐inflammatory effects of corticosteroids can be detected using our intradermal LPS challenge model, validating it for evaluation of future investigational drugs, as an initial assessment of the anti‐inflammatory effects of such compounds in a minimally invasive manner.</abstract><cop>United States</cop><pub>John Wiley and Sons Inc</pub><pmid>34935141</pmid><doi>10.1002/cpt.2516</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical pharmacology and therapeutics, 2022-04, Vol.111 (4), p.964-971 |
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| subjects | Adrenal Cortex Hormones Anti-Inflammatory Agents - therapeutic use Blister - drug therapy Clobetasol - pharmacology Clobetasol - therapeutic use Cytokines Drugs, Investigational Erythema - drug therapy Glucocorticoids - pharmacology Healthy Volunteers Humans Lipopolysaccharides Male Prednisolone - pharmacology |
| title | Clinical, Cellular, and Molecular Effects of Corticosteroids on the Response to Intradermal Lipopolysaccharide Administration in Healthy Volunteers |
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