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Soluble tumor necrosis factor receptors are released independent of TNF in endotoxemia

Medizinische Klinik I der Albert-Ludwigs-Universität and Max Planck Institut für Immunbiologie, D-79106 Freiburg, Germany

A. Seiz

Medizinische Klinik I der Albert-Ludwigs-Universität and Max Planck Institut für Immunbiologie, D-79106 Freiburg, Germany

C. Galanos

Medizinische Klinik I der Albert-Ludwigs-Universität and Max Planck Institut für Immunbiologie, D-79106 Freiburg, Germany

R. Mertelsmann

Medizinische Klinik I der Albert-Ludwigs-Universität and Max Planck Institut für Immunbiologie, D-79106 Freiburg, Germany

R. Engelhardt

Medizinische Klinik I der Albert-Ludwigs-Universität and Max Planck Institut für Immunbiologie, D-79106 Freiburg, Germany

The pathway by which the in vivo application of LPS induces the release of soluble TNF receptor molecules (sTNF-R) is not yet understood. Earlier findings have demonstrated that the injection of LPS induces the release of TNF, and injections of TNF induce sTNF-R I and II. Thus one would assume that sTNF-R are released after LPS application as a result of endogenous production of TNF. In this study, i.v. bolus injections of Salmonella abortus equi endotoxin (4 ng/kg body weight) once daily for 5 consecutive days were administered to cancer patients. The time course of serum levels of TNF and sTNF-R I and II were determined. sTNF-R I and II were released after every LPS injection with peak levels being comparable on days 1 through 5. In contrast, the TNF peak level on day 1 was about 50 times higher than on day 2. On days 3 through 5, no TNF could be detected, a phenomenon referred to as endotoxin tolerance. Since LPS was able to provoke a comparable release of sTNF-R despite inducing widely differing levels of TNF-, we conclude that the release of sTNF-R I and II during endotoxemia is not induced via TNF-.

Journal of Endotoxin Research, Vol. 2, No. 2, 85-89 (1995)
DOI: 10.1177/096805199500200202


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