Soluble interleukin 6 receptor is biologically active in vivo.
A cancer cell transfection model was used to evaluate biological activity of soluble IL-6 receptor (sIL-6R) in vivo. B-78 melanoma cells were stably transfected with cDNAs encoding human IL-6, murine sIL-6R and human leukaemia inhibitory factor (LIF). Control and transfected cells were intravenously (i.v.) and/or subcutaneously (s.c.) injected into B57BL/6 x C3H or SCID mice. Whereas B-78 cells formed tumours and lung metastasis in injected animals, transfected animals, transfected cells showed greatly reduced tumour and metastasis formation. Transfection of IL-6, sIL-6R or LIF had similar protective effects. The combination of IL-6 and sIL-6R was most effective. Kinetic analysis demonstrated a 3 week lag period between formation of tumours by B-78 cells and the combination of B-78 cells transfected with IL-6 and sIL-6R. No such lag phase was seen when B-78-IL-6 or B-78-IL-6 or B-78-sIL-6R were injected alone. These results indicate that IL-6 alone exhibits a different quality of activity when compared to the IL-6-soluble receptor complex. Our results demonstrate for the first time that sIL-6R is a biologically active molecule in vivo.
Mackiewicz
A
A
Department of Cancer Immunology, Great Poland Cancer Center, Poznan.
Wiznerowicz
M
M
Roeb
E
E
Karczewska
A
A
Nowak
J
J
Heinrich
P C
PC
Rose-John
S
S
D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D018076:DNA, Complementary; D015870:Gene Expression; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism; D007700:Kinetics; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology / Q000556:secondary*; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D014176:Protein Biosynthesis; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000378:metabolism; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2; D019714:Tissue Inhibitor of Metalloproteinases; D014162:Transfection
D018076:DNA, Complementary; D006023:Glycoproteins; D015850:Interleukin-6; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D018799:Intercellular Adhesion Molecule-1; D019716:Tissue Inhibitor of Metalloproteinase-2