Endotoxin induction of hepatic metallothionein is mediated through cytokines*1

摘要: Metallothionein (MT), a low molecular-weight, cysteine-rich, metal-binding protein, is induced by many environmental factors and variety of stimuli. Bacterial endotoxin (lipopolysaccharide, LPS) injection experimentally used to produce acute stress an effective inducer hepatic MT. However, the mechanism LPS induction MT not known. In present studies, we two substrains mice, differing in their production cytokines after administration, test hypothesis that mediated through cytokines. Normal (C3Heb/FeJ) cytokine-producing (C3H/HeJ) mice were given various doses LPS, interleukin-1 (IL-1), interleukin-6 (IL-6), or tumor necrosis factor (TNF), was determined 24 hr later Cd/hemoglobin assay. The low-cytokine-producing much less responsive (50 vs 150 micrograms MT/g liver 1.0 mg LPS/kg, ip) than normal but equally IL-1 (0.03-1.0 microgram/mouse). IL-6 (0.5-5.0 micrograms/mouse), TNF (0.005-0.5 All produced dose-dependent increase levels these murine (up five- sevenfold over controls). conclusion, data suggest may be