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Innate Immunity
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Factors involved in early in vitro endotoxin hyporesponsiveness in human endotoxemia

A. Nikola Kimmings

Department of Surgery, Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research

Dasja Pajkrt

Laboratory of Experimental Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands

Krista Zaaijer

Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research

Thybout M. Moojen

Department of Surgery, Laboratory of Experimental Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands

John K. Meenan

Laboratory of Experimental Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands

Jan W. ten Cate

Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research

Sander J.H. van Deventer

Laboratory of Experimental Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands

Sepsis and endotoxemia induce a state of early tolerance to the biological effects of endotoxin. Relatively little is known about the mechanisms or mediators involved in this endotoxin hyporesponsiveness. In this study endotoxin-induced TNF production of whole blood obtained at different time points from endotoxin challenged volunteers, and endotoxin- and PHA-induced TNF production by healthy PBMNCs in the presence of serum from endotoxin challenged volunteers were compared.

Endotoxin-induced TNF production by whole blood was found to be significantly reduced at 2 h after in vivo endotoxin administration, returning to baseline levels at t = 6 h. In addition, a reduction of TNF produced by healthy PBMNCs in the presence of post-endotoxin serum was observed. No correlation was found with the concentration of any of the well described anti-inflammatory mediators investigated nor with plasma levels of endotoxin-binding proteins.

Innate Immunity, Vol. 3, No. 4, 283-289 (1996)
DOI: 10.1177/096805199600300401
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