Liver regeneration induced by a designer human IL-6/sIL-6R fusion protein reverses severe hepatocellular injury.
The cytokine IL-6 plays a significant role in liver regeneration in conjunction with additional growth factors (HGF, TNF-alpha, and TGF-alpha). 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
E
Goldyne Savad Institute of Gene Therapy, Hadassah University Hospital, Jerusalem, Israel.
Zeira
E
E
Pappo
O
O
Peters
M
M
Rose-John
S
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D005688:Galactosamine / Q000633:toxicity; D006801:Humans; D015850:Interleukin-6 / Q000819:agonists* / Q000627:therapeutic use*; D017093:Liver Failure / Q000188:drug therapy*; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D018123:Receptors, Interleukin / Q000627:therapeutic use*; D019947:Receptors, Interleukin-6; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D013853:Thioacetamide / Q000633:toxicity
D015850:Interleukin-6; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D011993:Recombinant Fusion Proteins; C104543:interleukin 6-interleukin 6 receptor fusion protein, recombinant; D013853:Thioacetamide; D005688:Galactosamine