Soluble interleukin-6 receptor (sIL-6R) makes IL-6R negative T cell line respond to IL-6; it inhibits TNF production

The receptor for interleukin-6 (IL-6) consists of two subunits: a ligand sp ecific IL-6R alpha. and gp130 that is responsible for si,signal-transductio n. A soluble form of the ligand specific chain was described that when comp lexed to IL-6 is capable of binding to the membrane-bound gp130 subunit and thus can elicit signal-transduction. This soluble receptor can act on cell s that express only the gp130 but not the ligand-specific subunit of the IL -6R. This phenomenon, called trans-signaling, introduced a novel aspect of cytokine action. In this study we examined the response of Jurkat cells, th at are known not to express IL-6R alpha, to IL-6, the soluble IL-6 receptor (sIL-6R) and a covalent complex of IL-6 and sIL-6R termed Hyper-IL-6. We s tudied the expression of tumour necrosis factor (TNF) and interferon-gamma (IFN-gamma). The complex of IL-6+sIL-6R and Hyper-IL-6 inhibited significan tly the production of TNF in a gp130-dependent manner, whereas no differenc es in IFN-gamma expression were found. IL-6 and sIL-6R alone were not effec tive. Because we did not detect major differences in the TNF mRNA levels up on treatments, we conclude that the inhibition of TNF production should occ ur at the post-transcriptional level. These results provide another example of trans-signaling and underline the physiological importance of sIL-6R; a nd in the case of Hyper-IL-6 its possible therapeutic application can also be considered. (C) 2000 Elsevier Science B.V. All rights reserved.