Retarded liver growth in interleukin-6-deficient and tumor necrosis factorreceptor-1-deficient mice

The liver size in adult mammals is tightly regulated in relation to body we ight, 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 live r 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 prote in were decreased compared with those in age-matched wild-type mice. Weight s of other visceral organs were unaffected. Older adult (6- to 8-month-old) TNF receptor-1 knockout (TNFR1(-/-)) mice displayed decreased relative liv er weight. Treatment with a single injection of IL-6 increased liver wet an d dry weights in IL-6(-/-) and wild type mice, but not TNFR1(-/-) mice. Tre atment with TNF alpha enhanced liver weight and DNA synthesis of nonparench ymal liver cells at 24 h in wild-type, but not IL-6(-/-) mice. At 48 h, TNF alpha induced DNA synthesis in nonparenchymal cells and hepatocytes of bot h wild-type and IL-6(-/-) mice. In conclusion, TNF receptor-1 stimulation a nd IL-6 production are both necessary for normal liver weight gain in older adult mice. The results of TNF alpha and IL-6 treatment further indicate t hat the effects of TNF receptor-1 and IL-6 depend on each other for full st imulation of liver growth.