Metabolic deviation of mouse liver by RhIL1-alpha or RhTNF/cachectin.
In this work deviation of liver metabolism by cytokines, especially recombinant human interleukin 1-alpha (rhIL1-alpha), was investigated. Administration of rhIL1-alpha or recombinant human tumor necrosis factor (rhTNF/cachectin) to normal mice resulted in rapid, dose-dependent induction of high liver ornithine decarboxylase (ODC) activity. The effects of these cytokines on liver ODC were not indirect effects mediated by eicosanoids. The induction of liver ODC by rhIL1-alpha was at least partly a direct effect on hepatocytes, and was due to increase in de novo synthesis of the enzyme protein after increase in ODC mRNA. No specific protein was required for increase in the level of ODC-mRNA. On IL1 treatment, actinomycin D caused superinduction of liver ODC, which was at least partly due to increased stability of the ODC enzyme, because actinomycin D doubled the apparent half-life (from 50 to 95 min). Daily administration of 2 x 10(3) U of rhIL1-alpha to mice for 3 days also caused decrease in the level of the differentiated type of pyruvate kinase isozyme (PK-L) and marked increase in that of the prototype isozyme (PK-M2) in the liver, but did not cause significant change in the isozyme patterns of the kidney, thymus, and spleen. RhIL1-alpha also induced hypertrophy of the spleen. These results indicate that rhIL1-alpha causes metabolic deviation of the liver similar to that in tumor-bearing hosts.
Imamura
K
K
Department of Nutrition and Physiological Chemistry, Osaka University Medical School.
Wang
Z
Z
Murayama-Oda
K
K
Kim
H K
HK
Tanaka
T
T
D000818:Animals; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004790:Enzyme Induction; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009955:Ornithine Decarboxylase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011061:Poly A / Q000235:genetics / Q000302:isolation & purification; D011770:Pyruvate Kinase / Q000378:metabolism*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D007527:Isoenzymes; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D011061:Poly A; D012313:RNA; D003513:Cycloheximide; D011770:Pyruvate Kinase; D009955:Ornithine Decarboxylase