Induction of hepatic metallothioneins in tumor-bearing IL-6-null mice.
Interleukin-6 (IL-6) has been thought to play a key role in the induction of hepatic metallothionein (MT) synthesis in tumor-bearing animals. In order to clarify the role of IL-6 and to distinguish its effect from those of other cytokines, we inoculated IL-6-null and B6J129Sv (wild-type control) mice SC with 1 x 10(7) Ehrlich carcinoma cells and examined tumor growth, hepatic MT, and serum cytokines. We have found that tumor growth was followed by an increase of hepatic MT in both IL-6-null and wild-type mice and that the two strains of mice had a similar hepatic MT induction followed by zinc accumulation in the liver. These results could be explained by our finding that tumor-bearing IL-6-null mice had a high level of tumor-secreted IL-6 in the blood. In conclusion, by utilizing tumor-bearing IL-6-null mice, we have demonstrated that IL-6 secreted from the tumor cells is responsible for the tumor-evoked increase of hepatic MT level.
Molotkov
A
A
Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba, Japan.
Satoh
M
M
Tohyama
C
C
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D015850:Interleukin-6 / Q000235:genetics* / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008668:Metallothionein / Q000096:biosynthesis*; D051379:Mice; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism; D013997:Time Factors; D015032:Zinc / Q000378:metabolism
D016207:Cytokines; D015850:Interleukin-6; D003300:Copper; D008668:Metallothionein; D015032:Zinc