A NOVEL IL-18BP ELISA SHOWS ELEVATED SERUM IL-18BP IN SEPSIS AND EXTENSIVE DECREASE OF FREE IL-18
IL-18 binding protein (IL-18BP) is a circulating antagonist of the proinflammatory Th1 cytokine IL-18. It effectively blocks IL-18 by forming a 1:1 high affinity (Kd=400pM) complex, exhibiting a very low dissociation rate. We have developed a sandwich ELISA for IL-18BPa and determined its limit of d...
Gespeichert in:
| Veröffentlicht in: | Cytokine (Philadelphia, Pa.) Pa.), 2001-06, Vol.14 (6), p.334-342 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 342 |
|---|---|
| container_issue | 6 |
| container_start_page | 334 |
| container_title | Cytokine (Philadelphia, Pa.) |
| container_volume | 14 |
| creator | Novick, Daniela Schwartsburd, Boris Pinkus, Ron Suissa, Dan Belzer, Ilana Sthoeger, Zev Keane, William F. Chvatchko, Yolande Kim, Soo-Hyun Fantuzzi, Giamila Dinarello, Charles A. Rubinstein, Menachem |
| description | IL-18 binding protein (IL-18BP) is a circulating antagonist of the proinflammatory Th1 cytokine IL-18. It effectively blocks IL-18 by forming a 1:1 high affinity (Kd=400pM) complex, exhibiting a very low dissociation rate. We have developed a sandwich ELISA for IL-18BPa and determined its limit of detection (62pg/ml). Interference by IL-18 and related cytokines, as well as cross reactivity with other IL-18BP isoforms (b, c, and d) were determined. Using this ELISA, we measured serum IL-18BPa in large cohorts of healthy individuals and in septic patients. Serum IL-18BPa in healthy individuals was 2.15±0.15ng/ml (range 0.5–7ng/ml). In sepsis, the level rose to 21.9±1.44ng/ml (range 4–132ng/ml). Total IL-18 was measured in the same sera by an electrochemiluminescence assay and free IL-18 was calculated based on the mass action law. Total IL-18 was low in healthy individuals (64±17pg/ml) and most of it (∼85%) was in its free form. Total IL-18 and IL-18BPa were both elevated in sepsis patients upon admission (1.5±0.4ng/ml and 28.6±4.5ng/ml, respectively). At these levels, most of the IL-18 is bound to IL-18BPa, however the remaining free IL-18 is still higher than in healthy individuals. We conclude that IL-18BPa considerably inhibits circulating IL-18 in sepsis. Yet, exogenous administration of IL-18BPa may further reduce circulating IL-18 activity. |
| doi_str_mv | 10.1006/cyto.2001.0914 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_71079741</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1043466601909147</els_id><sourcerecordid>71079741</sourcerecordid><originalsourceid>FETCH-LOGICAL-c406t-dcc5535b789569e7dbbb19bf1a71c3fa0af9d98f47a8f1c919d9afe84b7e40923</originalsourceid><addsrcrecordid>eNp1kM9PwjAUxxujEUSvHk1P3oavrKzrcUKRJZMRBuit6boumQGm6zDhv3fLiJ48vR_5vG_yPgjdExgSAO9Jn-pyOAIgQ-CEXqA-Ae45ACP3su2p61DP83roxtoPAOAuY9eoRwjljHLaRyrAi3grIhxGDvGfl1hEYRLgZB6_JU0vtsFaTHEiVpvXXyRcNItlEiY4WEyxeF-LRRJuBZ6KyUoEicDxDM9WQnQHt-gqVztr7s51gDYzsZ7MnSh-CSdB5GgKXu1kWo_H7jhlPh973LAsTVPC05woRrSbK1A5z7ifU6b8nGhOmknlxqcpMxT4yB2gxy73syq_jsbWcl9YbXY7dTDl0UpGgDVPkwYcdqCuSmsrk8vPqtir6iQJyFaqbKXKVqpspTYHD-fkY7o32R9-ttgAfgeY5r_vwlTS6sIctMmKyuhaZmXxX_YPQyx81Q</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>71079741</pqid></control><display><type>article</type><title>A NOVEL IL-18BP ELISA SHOWS ELEVATED SERUM IL-18BP IN SEPSIS AND EXTENSIVE DECREASE OF FREE IL-18</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Novick, Daniela ; Schwartsburd, Boris ; Pinkus, Ron ; Suissa, Dan ; Belzer, Ilana ; Sthoeger, Zev ; Keane, William F. ; Chvatchko, Yolande ; Kim, Soo-Hyun ; Fantuzzi, Giamila ; Dinarello, Charles A. ; Rubinstein, Menachem</creator><creatorcontrib>Novick, Daniela ; Schwartsburd, Boris ; Pinkus, Ron ; Suissa, Dan ; Belzer, Ilana ; Sthoeger, Zev ; Keane, William F. ; Chvatchko, Yolande ; Kim, Soo-Hyun ; Fantuzzi, Giamila ; Dinarello, Charles A. ; Rubinstein, Menachem</creatorcontrib><description>IL-18 binding protein (IL-18BP) is a circulating antagonist of the proinflammatory Th1 cytokine IL-18. It effectively blocks IL-18 by forming a 1:1 high affinity (Kd=400pM) complex, exhibiting a very low dissociation rate. We have developed a sandwich ELISA for IL-18BPa and determined its limit of detection (62pg/ml). Interference by IL-18 and related cytokines, as well as cross reactivity with other IL-18BP isoforms (b, c, and d) were determined. Using this ELISA, we measured serum IL-18BPa in large cohorts of healthy individuals and in septic patients. Serum IL-18BPa in healthy individuals was 2.15±0.15ng/ml (range 0.5–7ng/ml). In sepsis, the level rose to 21.9±1.44ng/ml (range 4–132ng/ml). Total IL-18 was measured in the same sera by an electrochemiluminescence assay and free IL-18 was calculated based on the mass action law. Total IL-18 was low in healthy individuals (64±17pg/ml) and most of it (∼85%) was in its free form. Total IL-18 and IL-18BPa were both elevated in sepsis patients upon admission (1.5±0.4ng/ml and 28.6±4.5ng/ml, respectively). At these levels, most of the IL-18 is bound to IL-18BPa, however the remaining free IL-18 is still higher than in healthy individuals. We conclude that IL-18BPa considerably inhibits circulating IL-18 in sepsis. Yet, exogenous administration of IL-18BPa may further reduce circulating IL-18 activity.</description><identifier>ISSN: 1043-4666</identifier><identifier>EISSN: 1096-0023</identifier><identifier>DOI: 10.1006/cyto.2001.0914</identifier><identifier>PMID: 11497494</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Alternative Splicing ; Animals ; Antibodies, Monoclonal - metabolism ; Binding Sites ; COS Cells ; Dose-Response Relationship, Drug ; Enzyme-Linked Immunosorbent Assay - methods ; Glutathione Transferase - metabolism ; Glycoproteins - blood ; Glycoproteins - urine ; Humans ; Hybridomas - metabolism ; Intercellular Signaling Peptides and Proteins ; Interleukin-18 - blood ; interleukin-18/interleukin-18BP/ELISA/sepsis ; Kinetics ; Ligands ; Mice ; Protein Isoforms ; Radioimmunoassay ; Recombinant Fusion Proteins - metabolism ; Sepsis - blood</subject><ispartof>Cytokine (Philadelphia, Pa.), 2001-06, Vol.14 (6), p.334-342</ispartof><rights>2001 Academic Press</rights><rights>Copyright 2001 Academic Press.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c406t-dcc5535b789569e7dbbb19bf1a71c3fa0af9d98f47a8f1c919d9afe84b7e40923</citedby><cites>FETCH-LOGICAL-c406t-dcc5535b789569e7dbbb19bf1a71c3fa0af9d98f47a8f1c919d9afe84b7e40923</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1043466601909147$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11497494$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Novick, Daniela</creatorcontrib><creatorcontrib>Schwartsburd, Boris</creatorcontrib><creatorcontrib>Pinkus, Ron</creatorcontrib><creatorcontrib>Suissa, Dan</creatorcontrib><creatorcontrib>Belzer, Ilana</creatorcontrib><creatorcontrib>Sthoeger, Zev</creatorcontrib><creatorcontrib>Keane, William F.</creatorcontrib><creatorcontrib>Chvatchko, Yolande</creatorcontrib><creatorcontrib>Kim, Soo-Hyun</creatorcontrib><creatorcontrib>Fantuzzi, Giamila</creatorcontrib><creatorcontrib>Dinarello, Charles A.</creatorcontrib><creatorcontrib>Rubinstein, Menachem</creatorcontrib><title>A NOVEL IL-18BP ELISA SHOWS ELEVATED SERUM IL-18BP IN SEPSIS AND EXTENSIVE DECREASE OF FREE IL-18</title><title>Cytokine (Philadelphia, Pa.)</title><addtitle>Cytokine</addtitle><description>IL-18 binding protein (IL-18BP) is a circulating antagonist of the proinflammatory Th1 cytokine IL-18. It effectively blocks IL-18 by forming a 1:1 high affinity (Kd=400pM) complex, exhibiting a very low dissociation rate. We have developed a sandwich ELISA for IL-18BPa and determined its limit of detection (62pg/ml). Interference by IL-18 and related cytokines, as well as cross reactivity with other IL-18BP isoforms (b, c, and d) were determined. Using this ELISA, we measured serum IL-18BPa in large cohorts of healthy individuals and in septic patients. Serum IL-18BPa in healthy individuals was 2.15±0.15ng/ml (range 0.5–7ng/ml). In sepsis, the level rose to 21.9±1.44ng/ml (range 4–132ng/ml). Total IL-18 was measured in the same sera by an electrochemiluminescence assay and free IL-18 was calculated based on the mass action law. Total IL-18 was low in healthy individuals (64±17pg/ml) and most of it (∼85%) was in its free form. Total IL-18 and IL-18BPa were both elevated in sepsis patients upon admission (1.5±0.4ng/ml and 28.6±4.5ng/ml, respectively). At these levels, most of the IL-18 is bound to IL-18BPa, however the remaining free IL-18 is still higher than in healthy individuals. We conclude that IL-18BPa considerably inhibits circulating IL-18 in sepsis. Yet, exogenous administration of IL-18BPa may further reduce circulating IL-18 activity.</description><subject>Alternative Splicing</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - metabolism</subject><subject>Binding Sites</subject><subject>COS Cells</subject><subject>Dose-Response Relationship, Drug</subject><subject>Enzyme-Linked Immunosorbent Assay - methods</subject><subject>Glutathione Transferase - metabolism</subject><subject>Glycoproteins - blood</subject><subject>Glycoproteins - urine</subject><subject>Humans</subject><subject>Hybridomas - metabolism</subject><subject>Intercellular Signaling Peptides and Proteins</subject><subject>Interleukin-18 - blood</subject><subject>interleukin-18/interleukin-18BP/ELISA/sepsis</subject><subject>Kinetics</subject><subject>Ligands</subject><subject>Mice</subject><subject>Protein Isoforms</subject><subject>Radioimmunoassay</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>Sepsis - blood</subject><issn>1043-4666</issn><issn>1096-0023</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kM9PwjAUxxujEUSvHk1P3oavrKzrcUKRJZMRBuit6boumQGm6zDhv3fLiJ48vR_5vG_yPgjdExgSAO9Jn-pyOAIgQ-CEXqA-Ae45ACP3su2p61DP83roxtoPAOAuY9eoRwjljHLaRyrAi3grIhxGDvGfl1hEYRLgZB6_JU0vtsFaTHEiVpvXXyRcNItlEiY4WEyxeF-LRRJuBZ6KyUoEicDxDM9WQnQHt-gqVztr7s51gDYzsZ7MnSh-CSdB5GgKXu1kWo_H7jhlPh973LAsTVPC05woRrSbK1A5z7ifU6b8nGhOmknlxqcpMxT4yB2gxy73syq_jsbWcl9YbXY7dTDl0UpGgDVPkwYcdqCuSmsrk8vPqtir6iQJyFaqbKXKVqpspTYHD-fkY7o32R9-ttgAfgeY5r_vwlTS6sIctMmKyuhaZmXxX_YPQyx81Q</recordid><startdate>20010621</startdate><enddate>20010621</enddate><creator>Novick, Daniela</creator><creator>Schwartsburd, Boris</creator><creator>Pinkus, Ron</creator><creator>Suissa, Dan</creator><creator>Belzer, Ilana</creator><creator>Sthoeger, Zev</creator><creator>Keane, William F.</creator><creator>Chvatchko, Yolande</creator><creator>Kim, Soo-Hyun</creator><creator>Fantuzzi, Giamila</creator><creator>Dinarello, Charles A.</creator><creator>Rubinstein, Menachem</creator><general>Elsevier Ltd</general><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>20010621</creationdate><title>A NOVEL IL-18BP ELISA SHOWS ELEVATED SERUM IL-18BP IN SEPSIS AND EXTENSIVE DECREASE OF FREE IL-18</title><author>Novick, Daniela ; Schwartsburd, Boris ; Pinkus, Ron ; Suissa, Dan ; Belzer, Ilana ; Sthoeger, Zev ; Keane, William F. ; Chvatchko, Yolande ; Kim, Soo-Hyun ; Fantuzzi, Giamila ; Dinarello, Charles A. ; Rubinstein, Menachem</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c406t-dcc5535b789569e7dbbb19bf1a71c3fa0af9d98f47a8f1c919d9afe84b7e40923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Alternative Splicing</topic><topic>Animals</topic><topic>Antibodies, Monoclonal - metabolism</topic><topic>Binding Sites</topic><topic>COS Cells</topic><topic>Dose-Response Relationship, Drug</topic><topic>Enzyme-Linked Immunosorbent Assay - methods</topic><topic>Glutathione Transferase - metabolism</topic><topic>Glycoproteins - blood</topic><topic>Glycoproteins - urine</topic><topic>Humans</topic><topic>Hybridomas - metabolism</topic><topic>Intercellular Signaling Peptides and Proteins</topic><topic>Interleukin-18 - blood</topic><topic>interleukin-18/interleukin-18BP/ELISA/sepsis</topic><topic>Kinetics</topic><topic>Ligands</topic><topic>Mice</topic><topic>Protein Isoforms</topic><topic>Radioimmunoassay</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>Sepsis - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Novick, Daniela</creatorcontrib><creatorcontrib>Schwartsburd, Boris</creatorcontrib><creatorcontrib>Pinkus, Ron</creatorcontrib><creatorcontrib>Suissa, Dan</creatorcontrib><creatorcontrib>Belzer, Ilana</creatorcontrib><creatorcontrib>Sthoeger, Zev</creatorcontrib><creatorcontrib>Keane, William F.</creatorcontrib><creatorcontrib>Chvatchko, Yolande</creatorcontrib><creatorcontrib>Kim, Soo-Hyun</creatorcontrib><creatorcontrib>Fantuzzi, Giamila</creatorcontrib><creatorcontrib>Dinarello, Charles A.</creatorcontrib><creatorcontrib>Rubinstein, Menachem</creatorcontrib><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>Cytokine (Philadelphia, Pa.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Novick, Daniela</au><au>Schwartsburd, Boris</au><au>Pinkus, Ron</au><au>Suissa, Dan</au><au>Belzer, Ilana</au><au>Sthoeger, Zev</au><au>Keane, William F.</au><au>Chvatchko, Yolande</au><au>Kim, Soo-Hyun</au><au>Fantuzzi, Giamila</au><au>Dinarello, Charles A.</au><au>Rubinstein, Menachem</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A NOVEL IL-18BP ELISA SHOWS ELEVATED SERUM IL-18BP IN SEPSIS AND EXTENSIVE DECREASE OF FREE IL-18</atitle><jtitle>Cytokine (Philadelphia, Pa.)</jtitle><addtitle>Cytokine</addtitle><date>2001-06-21</date><risdate>2001</risdate><volume>14</volume><issue>6</issue><spage>334</spage><epage>342</epage><pages>334-342</pages><issn>1043-4666</issn><eissn>1096-0023</eissn><abstract>IL-18 binding protein (IL-18BP) is a circulating antagonist of the proinflammatory Th1 cytokine IL-18. It effectively blocks IL-18 by forming a 1:1 high affinity (Kd=400pM) complex, exhibiting a very low dissociation rate. We have developed a sandwich ELISA for IL-18BPa and determined its limit of detection (62pg/ml). Interference by IL-18 and related cytokines, as well as cross reactivity with other IL-18BP isoforms (b, c, and d) were determined. Using this ELISA, we measured serum IL-18BPa in large cohorts of healthy individuals and in septic patients. Serum IL-18BPa in healthy individuals was 2.15±0.15ng/ml (range 0.5–7ng/ml). In sepsis, the level rose to 21.9±1.44ng/ml (range 4–132ng/ml). Total IL-18 was measured in the same sera by an electrochemiluminescence assay and free IL-18 was calculated based on the mass action law. Total IL-18 was low in healthy individuals (64±17pg/ml) and most of it (∼85%) was in its free form. Total IL-18 and IL-18BPa were both elevated in sepsis patients upon admission (1.5±0.4ng/ml and 28.6±4.5ng/ml, respectively). At these levels, most of the IL-18 is bound to IL-18BPa, however the remaining free IL-18 is still higher than in healthy individuals. We conclude that IL-18BPa considerably inhibits circulating IL-18 in sepsis. Yet, exogenous administration of IL-18BPa may further reduce circulating IL-18 activity.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>11497494</pmid><doi>10.1006/cyto.2001.0914</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1043-4666 |
| ispartof | Cytokine (Philadelphia, Pa.), 2001-06, Vol.14 (6), p.334-342 |
| issn | 1043-4666 1096-0023 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_71079741 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Alternative Splicing Animals Antibodies, Monoclonal - metabolism Binding Sites COS Cells Dose-Response Relationship, Drug Enzyme-Linked Immunosorbent Assay - methods Glutathione Transferase - metabolism Glycoproteins - blood Glycoproteins - urine Humans Hybridomas - metabolism Intercellular Signaling Peptides and Proteins Interleukin-18 - blood interleukin-18/interleukin-18BP/ELISA/sepsis Kinetics Ligands Mice Protein Isoforms Radioimmunoassay Recombinant Fusion Proteins - metabolism Sepsis - blood |
| title | A NOVEL IL-18BP ELISA SHOWS ELEVATED SERUM IL-18BP IN SEPSIS AND EXTENSIVE DECREASE OF FREE IL-18 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T09%3A25%3A42IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20NOVEL%20IL-18BP%20ELISA%20SHOWS%20ELEVATED%20SERUM%20IL-18BP%20IN%20SEPSIS%20AND%20EXTENSIVE%20DECREASE%20OF%20FREE%20IL-18&rft.jtitle=Cytokine%20(Philadelphia,%20Pa.)&rft.au=Novick,%20Daniela&rft.date=2001-06-21&rft.volume=14&rft.issue=6&rft.spage=334&rft.epage=342&rft.pages=334-342&rft.issn=1043-4666&rft.eissn=1096-0023&rft_id=info:doi/10.1006/cyto.2001.0914&rft_dat=%3Cproquest_cross%3E71079741%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=71079741&rft_id=info:pmid/11497494&rft_els_id=S1043466601909147&rfr_iscdi=true |