Metallothionein induction by restraint stress: Role of glucocorticoids andIL-6

Restraint stress increased liver metallothionein-I (MT-I) mRNA and MT-I+II protein levels. The glucocorticoid receptor antagonist RU 486 decreased thi s response. In contrast, adrenalectomy only decreased MT-I+II protein level s. Moreover, corticosterone or progesterone did not reverse the effect of R U 486, These results suggest that glucocorticoids are important for MT-I+II protein synthesis but not for MT-I mRNA accumulation during restraint stre ss, and that other factors must be involved in this process, Interleukin-6 (IL-6) deficient mice showed a significant decrease of restraint stress-ind uced liver MT-I mRNA levels (similar to 30% of IL-6+/+ mice) up to similar to 4-5 hours after the onset of stress. Western blotting of hepatic nuclear proteins showed that the IL-6 responsive transcription factor Stat3, which has been shown to mediate MT induction by inflammation, was also activated by restraint stress. Results after extended periods of restraint stress in dicate that IL-6 participates early and transiently in the process. The ana lysis of the expression of the acute phase plasma protein serum amyloid A s uggests that restraint stress elicits an acute phase response similar to th at caused by inflammation. (C) 2000 Academic Press.