¹Institute of Clinical Pharmacology, University of Leipzig, Härtelstrasse 16-18, Leipzig, Germany

Correspondence: Dr rer nat Heike Knüpfer, University of Leipzig, Institute of Clinical Pharmacology, Härtelstrasse 16-18, 04107 Leipzig, Germany. E-mail: Heike.Knuepfer@medizin.uni-leipzig.de

Received 22 February 2007; Revised 19 July 2007; Accepted 24 July 2007; Published online 28 August 2007.

Abstract

On target cells, interleukin-6 (IL-6) interacts with its receptor complex consisting of the membrane-bound IL-6 receptor (IL-6R) and the signal transducing protein gp130. IL-6R can exist as a soluble protein (sIL-6R), which binds the ligand IL-6. This soluble complex can bind to gp130 on cells that lack the membrane-bound IL-6R and initiate signaling. This process is named transsignaling. The significance of transsignaling via sIL-6R is underlined by different publications and exceeds very probably the significance of the membrane-bound IL-6R. It is the general assumption that sIL-6R acts as an agonist in combination with IL-6 resulting in an enhancement of the IL-6 effects. In this article, we suppose 'non-agonistic' properties. There are several publications that give reasons to speculate that sIL-6R (a) has IL-6-antagonistic effects, (b) has orphan properties and (c) interacts with yet unknown binding partners different from IL-6. Knowledge about additional properties of sIL-6R will enlarge the biologic understanding of this molecule and might give an explanation for the sometimes contrasting effects of the cytokine IL-6.