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Retarded Liver Growth in Interleukin-6-Deficient and Tumor Necrosis Factor Receptor-1-Deficient Mice¹

Research Center for Endocrinology and Metabolism, Departments of Internal Medicine (V.W., K.W., J.S., C.O., J.-O.J.) and Pathology (M.H.), Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden; and Basel Institute for Immunology (M.K.), CH-4005 Basel, Switzerland

Address all correspondence and requests for reprints to: V. Wallenius, M.D., Ph.D., Research Center for Endocrinology and Metabolism, Gröna Stråket 8, SE-413 45 Gothenburg, Sweden. E-mail: ville.wallenius{at}medic.gu.se

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 TNF enhanced liver weight and DNA synthesis of nonparenchymal liver cells at 24 h in wild-type, but not IL-6^-/-, mice. At 48 h, TNF 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 TNF 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.

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