title: Retarded liver growth in interleukin-6-deficient and tumor necrosis factor receptor-1-deficient mice.
abstract: The liver size in adult mammals is tightly regulated in relation to body weight, but the hormonal control of this is largely unknown. We investigated the roles of interleukin-6 (IL-6) and tumor necrosis factor (TNF) receptor-1 in the regulation of intact liver weight in adult mice. The relative liver wet and dry weights of older adult (5- to 10-month-old) IL-6 knockout (IL-6(-/-)) mice were decreased by 22-28%, and total contents of DNA and protein were decreased compared with those in age-matched wild-type mice. Weights of other visceral organs were unaffected. Older adult (6- to 8-month-old) TNF receptor-1 knockout (TNFR1(-/-)) mice displayed decreased relative liver weight. Treatment with a single injection of IL-6 increased liver wet and dry weights in IL-6(-/-) and wild-type mice, but not TNFR1(-/-) mice. Treatment with TNFalpha enhanced liver weight and DNA synthesis of nonparenchymal liver cells at 24 h in wild-type, but not IL-6(-/-), mice. At 48 h, TNFalpha induced DNA synthesis in nonparenchymal cells and hepatocytes of both wild-type and IL-6(-/-) mice. In conclusion, TNF receptor-1 stimulation and IL-6 production are both necessary for normal liver weight gain in older adult mice. The results of TNFalpha and IL-6 treatment further indicate that the effects of TNF receptor-1 and IL-6 depend on each other for full stimulation of liver growth.
authors: Research Center for Endocrinology and Metabolism, Department of Internal Medicine, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden. ville.wallenius@medic.gu.se
authors: V
authors: V
authors: Wallenius
authors: K
authors: K
authors: Wallenius
authors: M
authors: M
authors: Hisaoka
authors: J
authors: J
authors: Sandstedt
authors: C
authors: C
authors: Ohlsson
authors: M
authors: M
authors: Kopf
authors: J O
authors: JO
authors: Jansson
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D004247:DNA / Q000378:metabolism; D013006:Growth Hormone / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects / Q000254:growth & development*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009929:Organ Size / Q000502:physiology; D020033:Protein Isoforms / Q000172:deficiency / Q000235:genetics; D011506:Proteins / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency* / Q000235:genetics; D047888:Receptors, Tumor Necrosis Factor, Type I; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D015850:Interleukin-6; D020033:Protein Isoforms; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D013006:Growth Hormone; D004247:DNA