This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Derkx, H.H.F. Articles by van Deventer, S.J.H. Search for Related Content PubMed Articles by Derkx, H.H.F. Articles by van Deventer, S.J.H. Social Bookmarking                         What's this?

Familial differences in endotoxin-induced TNF release in whole blood and peripheral blood mononuclear cells in vitro; relationship to TNF gene polymorphism

Academic Medical Center, University of Amsterdam, Department of Pediatrics and Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, The Netherlands, The Ludwig Institute for Cancer Research, Epalinges, Switzerland, The Central Laboratory for the Blood Transfusion Services, Amsterdam, Academic Hospital Leiden, Department of Rheumatology, Department of Medical Statistics and Clinical Epidemiology, The Netherlands

K.F. Bruin

Academic Medical Center, University of Amsterdam, Department of Pediatrics and Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, The Netherlands, The Ludwig Institute for Cancer Research, Epalinges, Switzerland, The Central Laboratory for the Blood Transfusion Services, Amsterdam, Academic Hospital Leiden, Department of Rheumatology, Department of Medical Statistics and Clinical Epidemiology, The Netherlands

C.V. Jongeneel

Academic Medical Center, University of Amsterdam, Department of Pediatrics and Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, The Netherlands, The Ludwig Institute for Cancer Research, Epalinges, Switzerland, The Central Laboratory for the Blood Transfusion Services, Amsterdam, Academic Hospital Leiden, Department of Rheumatology, Department of Medical Statistics and Clinical Epidemiology, The Netherlands

L.P. de Waal

Academic Medical Center, University of Amsterdam, Department of Pediatrics and Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, The Netherlands, The Ludwig Institute for Cancer Research, Epalinges, Switzerland, The Central Laboratory for the Blood Transfusion Services, Amsterdam, Academic Hospital Leiden, Department of Rheumatology, Department of Medical Statistics and Clinical Epidemiology, The Netherlands

B.M.N. Brinkman

Academic Medical Center, University of Amsterdam, Department of Pediatrics and Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, The Netherlands, The Ludwig Institute for Cancer Research, Epalinges, Switzerland, The Central Laboratory for the Blood Transfusion Services, Amsterdam, Academic Hospital Leiden, Department of Rheumatology, Department of Medical Statistics and Clinical Epidemiology, The Netherlands

C.L. Verweij

Academic Medical Center, University of Amsterdam, Department of Pediatrics and Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, The Netherlands, The Ludwig Institute for Cancer Research, Epalinges, Switzerland, The Central Laboratory for the Blood Transfusion Services, Amsterdam, Academic Hospital Leiden, Department of Rheumatology, Department of Medical Statistics and Clinical Epidemiology, The Netherlands

J.J. Houwing-Duistermaat

Academic Medical Center, University of Amsterdam, Department of Pediatrics and Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, The Netherlands, The Ludwig Institute for Cancer Research, Epalinges, Switzerland, The Central Laboratory for the Blood Transfusion Services, Amsterdam, Academic Hospital Leiden, Department of Rheumatology, Department of Medical Statistics and Clinical Epidemiology, The Netherlands

F.R. Rosendaal

Academic Medical Center, University of Amsterdam, Department of Pediatrics and Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, The Netherlands, The Ludwig Institute for Cancer Research, Epalinges, Switzerland, The Central Laboratory for the Blood Transfusion Services, Amsterdam, Academic Hospital Leiden, Department of Rheumatology, Department of Medical Statistics and Clinical Epidemiology, The Netherlands

S.J.H. van Deventer

Academic Medical Center, University of Amsterdam, Department of Pediatrics and Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, The Netherlands, The Ludwig Institute for Cancer Research, Epalinges, Switzerland, The Central Laboratory for the Blood Transfusion Services, Amsterdam, Academic Hospital Leiden, Department of Rheumatology, Department of Medical Statistics and Clinical Epidemiology, The Netherlands

Healthy volunteers show large interindividual differences in endotoxin-induced TNF release in vitro and certain HLA class II types can be related to phenotypic TNF resporise. To investigate the possibility of a genetic basis for endotoxin responsiveness, we tested TNF release in whole blood and PBMNC after stimulation by endotoxin in 47 relatives of 7 healthy volunteers. All volunteers were HLA-typed and the TNF-gene associated Nco1 and DNA microsatellite polymorphisms were determined.

A significant difference in TNF release by PBMNC and the Nco1 genotype could be established, showing a lower response of TNFB*2 homozygotes than TNFB*1 homozygotes (165 vs 265, 413 vs 703 and 462 vs 832 pg/106 PBMNC for 1, 10 and 100 ng/ml of endotoxin respectively; P < 0.05). The highest endotoxin-induced TNF release was observed in TNFB*1/TNFB*2 heterozygotes (340, 911 and 1,149 pg/10 ⁶ PBMNC respectively; P < 0.05 compared to TNFB*1 homozygotes and P < 0.0005 when compared to TNFB*2 homozygotes). TNFa and TNFb microsatellite typing revealed extensive polymorphism, showing a significantly lower TNF release in whole blood in individuals with TNFa2, -a6 and -a10 alleles than in individuals with TNFa4 and -a11 microsatellite haplotypes.

Journal of Endotoxin Research, Vol. 2, No. 1, 19-25 (1995)
DOI: 10.1177/096805199500200103


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?