Sensitization of target cells and increase of the plasma half- life of IL-6 in mice transgenic for the human soluble IL-6R. (A) Dose-response of the IL-6–induced hepatic acute phase protein expression. Haptoglobin expression in the liver of control mice (−/−) and heterozygous (−/+) and homozygous (+/+) mice was analyzed. Mice were injected intraperitoneally with various dosages of human IL-6 as indicated. Mice were killed 4 hours after injection. (B) Time course of the hepatic acute phase protein expression. Mice were injected intraperitoneally with 8 μg of human IL-6 and killed after the time periods indicated. Total RNA was prepared from the liver and subjected to Northern blot analysis. Filters were hybridized with a³²P-labeled 0.9-kb HinfI restriction fragment of human haptoglobin cDNA. (C) Serum levels of human IL-6 in control mice or heterozygous (−/+) or homozygous (+/+) transgenic mice expressing the human soluble IL-6R were measured 4 hours after injection with a human IL-6–specific ELISA.