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Liver regeneration induced by a designer human IL-6/sIL-6R fusion protein reverses severe hepatocellular injury

EITHAN GALUN^*,1, EVELYN ZEIRA^*,, ORIT PAPPO, MALTE PETERS^§ and STEFAN ROSE-JOHN

^* Goldyne Savad Institute of Gene Therapy,
Liver Unit, and
Department of Pathology Hadassah University Hospital, Jerusalem, Israel; and
^§ I. Medizinische Klinik, Abteilung Pathophysiologie, Johannes Gutenberg Universitat, Mainz, Germany

¹Correspondence: Goldyne Savad Institute of Gene Therapy; Hadassah University Hospital; Jerusalem 91120; Israel. E-mail: galun{at}md2.huji.ac.il

The cytokine IL-6 plays a significant role in liver regeneration in conjunction with additional growth factors (HGF, TNF-, and TGF-). Many IL-6 effects depend on a naturally occurring soluble IL-6 receptor (sIL-6R). Here, the chimeric protein hyper-IL-6, constructed from the human IL-6 protein fused to a truncated form of its receptor, was found to have superagonistic IL-6 properties, and as such, enhanced liver cell regeneration. Hyper-IL-6 reversed the state of hepatotoxicity and enhanced the survival rates of rats suffering from fulminant hepatic failure after D-galactosamine administration. The hyper-IL-6 protein has a significant potential for use in the treatment of severe human liver diseases.—Galun, E., Zeira, E., Pappo, O., Peters, M., Rose-John, S. Liver regeneration induced by a designer human IL-6/sIL-6R fusion protein reverses severe hepatocellular injury.

Key Words: interleukin 6 • chimeric protein • hyper-IL-6 • cytokines • hepatotoxicity • liver failure

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