n-hexane-induced synthesis of hepatic metallothionein is mediated by IL-6 in mouse.
The mechanism of metallothionein (MT) synthesis in the liver by n-hexane (HX) was examined. The increased synthesis of MT in the liver by HX was inhibited by dexamethasone pretreatment. Serum IL-6 was increased soon after HX injection, reaching a maximum at 8-16 hr, and then decreased, but neither IL-1 nor TNF was increased. The hepatic MT concentration reached a maximum later than did the serum IL-6 concentration, at 2 days after administration. When the MT synthesis induced by HX was inhibited by dexamethasone pretreatment, the concentration of IL-6 in the serum was suppressed to a very low level. Furthermore, the increase in concentration of hepatic MT and plasma fibrinogen was significantly decreased by the anti-mouse IL-6 monoclonal antibody. The concentration of hepatic MT was higher when the concentration of HX in the olive oil of the solution for injection was higher, even when the amount of HX administered was the same. It is suggested that the cytokine(s) is produced by the macrophage and fibroblast through injury and inflammation at the site of administration. These findings suggest that MT synthesis resulting from HX is induced indirectly through cytokine(s) production, especially IL-6.
Itoh
N
N
Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Japan.
Okamoto
H
H
Ohta
M
M
Hori
T
T
Min
K S
KS
Onosaka
S
S
Nakanishi
H
H
Okabe
M
M
Muto
N
N
Tanaka
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D005340:Fibrinogen / Q000378:metabolism; D006586:Hexanes / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D015850:Interleukin-6 / Q000097:blood / Q000502:physiology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis*; D051379:Mice
D000911:Antibodies, Monoclonal; D006586:Hexanes; D015850:Interleukin-6; C026385:n-hexane; D003907:Dexamethasone; D005340:Fibrinogen; D008668:Metallothionein