Nonspecific Human IgG Reduces Survival in Neonatal Rats Infected with Escherichia coli
Human intravenous IgG (IVIG) containing specific antibodies protects neonatal rats from septic death. However, IVIG has immunosuppressive properties and clinical trials of IVIG in neonates at risk for sepsis have yielded conflicting results. This study was designed to test the hypothesis that nonspe...
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| Veröffentlicht in: | The American journal of the medical sciences 2001-09, Vol.322 (3), p.141-144 |
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| creator | Cole, Cameron W. Jung, Erzsebet Lassiter, Herbert A. Feldhoff, Richard C. Goldsmith, L. Jane Wilson, Richard A. |
| description | Human intravenous IgG (IVIG) containing specific antibodies protects neonatal rats from septic death. However, IVIG has immunosuppressive properties and clinical trials of IVIG in neonates at risk for sepsis have yielded conflicting results.
This study was designed to test the hypothesis that nonspecific antibodies in IVIG reduce survival in neonatal rats infected with Escherichia coli.
Specific antibodies were adsorbed from IVIG with E coli to produce IVIG/anti-E coli −. After transthoracic administration of E coli, survival was determined in neonatal rats injected intraperitoneally with phosphate-buffered saline, IVIG/anti-E coli − (500mg/kg) or IVIG containing anti-E coli antibodies (IVIG/anti-E coli +). Complement-mediated hemolytic activity of neonatal rat serum was quantified using sensitized sheep erythrocytes.
Compared with placebo, intraperitoneal IVIG/anti-E coli − reduced neonatal survival after E coli infection. In contrast, IVIG/anti-E coli + protected infected animals. Both IVIG/anti-E coli − and IVIG/anti-E coli + impaired the complement-mediated hemolytic activity of neonatal rat serum.
IVIG contained (1) nonspecific antibodies that reduced survival in neonatal rats infected with E coli and (2) protective anti-E coli antibodies that enhanced survival in neonatal rats infected with E coli. We speculate that in clinical trials of IVIG to treat or prevent neonatal sepsis, inconsistent results may be caused, in part, by lot-to-lot variations in the ratio of immunosuppressive, nonspecific antibodies to protective, specific antibodies. |
| doi_str_mv | 10.1097/00000441-200109000-00006 |
| format | Article |
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This study was designed to test the hypothesis that nonspecific antibodies in IVIG reduce survival in neonatal rats infected with Escherichia coli.
Specific antibodies were adsorbed from IVIG with E coli to produce IVIG/anti-E coli −. After transthoracic administration of E coli, survival was determined in neonatal rats injected intraperitoneally with phosphate-buffered saline, IVIG/anti-E coli − (500mg/kg) or IVIG containing anti-E coli antibodies (IVIG/anti-E coli +). Complement-mediated hemolytic activity of neonatal rat serum was quantified using sensitized sheep erythrocytes.
Compared with placebo, intraperitoneal IVIG/anti-E coli − reduced neonatal survival after E coli infection. In contrast, IVIG/anti-E coli + protected infected animals. Both IVIG/anti-E coli − and IVIG/anti-E coli + impaired the complement-mediated hemolytic activity of neonatal rat serum.
IVIG contained (1) nonspecific antibodies that reduced survival in neonatal rats infected with E coli and (2) protective anti-E coli antibodies that enhanced survival in neonatal rats infected with E coli. We speculate that in clinical trials of IVIG to treat or prevent neonatal sepsis, inconsistent results may be caused, in part, by lot-to-lot variations in the ratio of immunosuppressive, nonspecific antibodies to protective, specific antibodies.</description><identifier>ISSN: 0002-9629</identifier><identifier>EISSN: 1538-2990</identifier><identifier>DOI: 10.1097/00000441-200109000-00006</identifier><identifier>PMID: 11570779</identifier><identifier>CODEN: AJMSA9</identifier><language>eng</language><publisher>Hagerstown, MD: Elsevier Inc</publisher><subject>Animals ; Animals, Newborn ; Antibodies, Bacterial - toxicity ; Antibody Specificity ; Biological and medical sciences ; Complement System Proteins - immunology ; Escherichia coli - immunology ; Escherichia coli Infections - immunology ; Escherichia coli Infections - prevention & control ; Escherichia coli Infections - therapy ; General aspects ; Hemolysis ; Human infectious diseases. Experimental studies and models ; Humans ; IgG ; Immunoglobulins, Intravenous - toxicity ; In Vitro Techniques ; Infectious diseases ; Intravenous immunoglobulin ; Medical sciences ; Neonatal sepsis ; Rats ; Rats, Sprague-Dawley</subject><ispartof>The American journal of the medical sciences, 2001-09, Vol.322 (3), p.141-144</ispartof><rights>2001 Southern Society for Clinical Investigation</rights><rights>Copyright © 2001 by the Southern Society for Clinical Investigation. Unauthorized reproduction of this article is prohibited.</rights><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4456-391149e244651fce268530d7254866e71be0f520be8149689c136d0ee85a923a3</citedby><cites>FETCH-LOGICAL-c4456-391149e244651fce268530d7254866e71be0f520be8149689c136d0ee85a923a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14061129$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11570779$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cole, Cameron W.</creatorcontrib><creatorcontrib>Jung, Erzsebet</creatorcontrib><creatorcontrib>Lassiter, Herbert A.</creatorcontrib><creatorcontrib>Feldhoff, Richard C.</creatorcontrib><creatorcontrib>Goldsmith, L. Jane</creatorcontrib><creatorcontrib>Wilson, Richard A.</creatorcontrib><title>Nonspecific Human IgG Reduces Survival in Neonatal Rats Infected with Escherichia coli</title><title>The American journal of the medical sciences</title><addtitle>Am J Med Sci</addtitle><description>Human intravenous IgG (IVIG) containing specific antibodies protects neonatal rats from septic death. However, IVIG has immunosuppressive properties and clinical trials of IVIG in neonates at risk for sepsis have yielded conflicting results.
This study was designed to test the hypothesis that nonspecific antibodies in IVIG reduce survival in neonatal rats infected with Escherichia coli.
Specific antibodies were adsorbed from IVIG with E coli to produce IVIG/anti-E coli −. After transthoracic administration of E coli, survival was determined in neonatal rats injected intraperitoneally with phosphate-buffered saline, IVIG/anti-E coli − (500mg/kg) or IVIG containing anti-E coli antibodies (IVIG/anti-E coli +). Complement-mediated hemolytic activity of neonatal rat serum was quantified using sensitized sheep erythrocytes.
Compared with placebo, intraperitoneal IVIG/anti-E coli − reduced neonatal survival after E coli infection. In contrast, IVIG/anti-E coli + protected infected animals. Both IVIG/anti-E coli − and IVIG/anti-E coli + impaired the complement-mediated hemolytic activity of neonatal rat serum.
IVIG contained (1) nonspecific antibodies that reduced survival in neonatal rats infected with E coli and (2) protective anti-E coli antibodies that enhanced survival in neonatal rats infected with E coli. We speculate that in clinical trials of IVIG to treat or prevent neonatal sepsis, inconsistent results may be caused, in part, by lot-to-lot variations in the ratio of immunosuppressive, nonspecific antibodies to protective, specific antibodies.</description><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Antibodies, Bacterial - toxicity</subject><subject>Antibody Specificity</subject><subject>Biological and medical sciences</subject><subject>Complement System Proteins - immunology</subject><subject>Escherichia coli - immunology</subject><subject>Escherichia coli Infections - immunology</subject><subject>Escherichia coli Infections - prevention & control</subject><subject>Escherichia coli Infections - therapy</subject><subject>General aspects</subject><subject>Hemolysis</subject><subject>Human infectious diseases. Experimental studies and models</subject><subject>Humans</subject><subject>IgG</subject><subject>Immunoglobulins, Intravenous - toxicity</subject><subject>In Vitro Techniques</subject><subject>Infectious diseases</subject><subject>Intravenous immunoglobulin</subject><subject>Medical sciences</subject><subject>Neonatal sepsis</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><issn>0002-9629</issn><issn>1538-2990</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9PwyAYh4nRuDn9CoaLxypQSstRl7ktWTSZf64No28t2rULtFv89lI73cnIBfjled6EHwhhSq4pkfEN6RbnNGCE-MBfgi4RR2hIozAJmJTkGA19xAIpmBygM-fePcsSGp6iAaVRTOJYDtHrQ125DWiTG41n7VpVeP42xUvIWg0OP7V2a7aqxKbCD1BXqvHnpWocnlc56AYyvDNNgSdOF2CNLozCui7NOTrJVengYr-P0Mv95Hk8CxaP0_n4dhFoziMRhJJSLoFxLiKaa2AiiUKSxSziiRAQ0xWQPGJkBYnnRCI1DUVGAJJISRaqcISSfq62tXMW8nRjzVrZz5SStKsq_akq_a3qOxJevezVTbtaQ3YQ99144GoPKKdVmVtVaeMOHCeCUtZxvOd2ddmAdR9luwObFqDKpkj_-iqv3fUa-H62xhtOG6g0ZMb6ZtOsNv8_4gvTLpKS</recordid><startdate>200109</startdate><enddate>200109</enddate><creator>Cole, Cameron W.</creator><creator>Jung, Erzsebet</creator><creator>Lassiter, Herbert A.</creator><creator>Feldhoff, Richard C.</creator><creator>Goldsmith, L. Jane</creator><creator>Wilson, Richard A.</creator><general>Elsevier Inc</general><general>Copyright by the Southern Society for Clinical Investigation. Unauthorized reproduction of this article is prohibited</general><general>Lippincott</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></search><sort><creationdate>200109</creationdate><title>Nonspecific Human IgG Reduces Survival in Neonatal Rats Infected with Escherichia coli</title><author>Cole, Cameron W. ; Jung, Erzsebet ; Lassiter, Herbert A. ; Feldhoff, Richard C. ; Goldsmith, L. Jane ; Wilson, Richard A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4456-391149e244651fce268530d7254866e71be0f520be8149689c136d0ee85a923a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Antibodies, Bacterial - toxicity</topic><topic>Antibody Specificity</topic><topic>Biological and medical sciences</topic><topic>Complement System Proteins - immunology</topic><topic>Escherichia coli - immunology</topic><topic>Escherichia coli Infections - immunology</topic><topic>Escherichia coli Infections - prevention & control</topic><topic>Escherichia coli Infections - therapy</topic><topic>General aspects</topic><topic>Hemolysis</topic><topic>Human infectious diseases. Experimental studies and models</topic><topic>Humans</topic><topic>IgG</topic><topic>Immunoglobulins, Intravenous - toxicity</topic><topic>In Vitro Techniques</topic><topic>Infectious diseases</topic><topic>Intravenous immunoglobulin</topic><topic>Medical sciences</topic><topic>Neonatal sepsis</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cole, Cameron W.</creatorcontrib><creatorcontrib>Jung, Erzsebet</creatorcontrib><creatorcontrib>Lassiter, Herbert A.</creatorcontrib><creatorcontrib>Feldhoff, Richard C.</creatorcontrib><creatorcontrib>Goldsmith, L. Jane</creatorcontrib><creatorcontrib>Wilson, Richard A.</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><jtitle>The American journal of the medical sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cole, Cameron W.</au><au>Jung, Erzsebet</au><au>Lassiter, Herbert A.</au><au>Feldhoff, Richard C.</au><au>Goldsmith, L. Jane</au><au>Wilson, Richard A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nonspecific Human IgG Reduces Survival in Neonatal Rats Infected with Escherichia coli</atitle><jtitle>The American journal of the medical sciences</jtitle><addtitle>Am J Med Sci</addtitle><date>2001-09</date><risdate>2001</risdate><volume>322</volume><issue>3</issue><spage>141</spage><epage>144</epage><pages>141-144</pages><issn>0002-9629</issn><eissn>1538-2990</eissn><coden>AJMSA9</coden><abstract>Human intravenous IgG (IVIG) containing specific antibodies protects neonatal rats from septic death. However, IVIG has immunosuppressive properties and clinical trials of IVIG in neonates at risk for sepsis have yielded conflicting results.
This study was designed to test the hypothesis that nonspecific antibodies in IVIG reduce survival in neonatal rats infected with Escherichia coli.
Specific antibodies were adsorbed from IVIG with E coli to produce IVIG/anti-E coli −. After transthoracic administration of E coli, survival was determined in neonatal rats injected intraperitoneally with phosphate-buffered saline, IVIG/anti-E coli − (500mg/kg) or IVIG containing anti-E coli antibodies (IVIG/anti-E coli +). Complement-mediated hemolytic activity of neonatal rat serum was quantified using sensitized sheep erythrocytes.
Compared with placebo, intraperitoneal IVIG/anti-E coli − reduced neonatal survival after E coli infection. In contrast, IVIG/anti-E coli + protected infected animals. Both IVIG/anti-E coli − and IVIG/anti-E coli + impaired the complement-mediated hemolytic activity of neonatal rat serum.
IVIG contained (1) nonspecific antibodies that reduced survival in neonatal rats infected with E coli and (2) protective anti-E coli antibodies that enhanced survival in neonatal rats infected with E coli. We speculate that in clinical trials of IVIG to treat or prevent neonatal sepsis, inconsistent results may be caused, in part, by lot-to-lot variations in the ratio of immunosuppressive, nonspecific antibodies to protective, specific antibodies.</abstract><cop>Hagerstown, MD</cop><pub>Elsevier Inc</pub><pmid>11570779</pmid><doi>10.1097/00000441-200109000-00006</doi><tpages>4</tpages></addata></record> |
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| subjects | Animals Animals, Newborn Antibodies, Bacterial - toxicity Antibody Specificity Biological and medical sciences Complement System Proteins - immunology Escherichia coli - immunology Escherichia coli Infections - immunology Escherichia coli Infections - prevention & control Escherichia coli Infections - therapy General aspects Hemolysis Human infectious diseases. Experimental studies and models Humans IgG Immunoglobulins, Intravenous - toxicity In Vitro Techniques Infectious diseases Intravenous immunoglobulin Medical sciences Neonatal sepsis Rats Rats, Sprague-Dawley |
| title | Nonspecific Human IgG Reduces Survival in Neonatal Rats Infected with Escherichia coli |
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