Abstract: | A universal component of inflammation is the increased synthesis of a series of plasma proteins (acute-phase proteins) by the liver. The postulated messenger of acute-phase protein induction is released by leucocytes at the site of inflammation and has been shown to co-purify with endogenous pyrogen or lymphocyte-activating factor. Interleukin-1, molecular weight 17,000, pI 6 X 8-7 X 2, was purified to homogeneity from adherent human blood monocytes by a combination of affinity chromatography, gel filtration and isoelectric focusing. We examined the direct effect of pure IL-1 on the induction of acute-phase protein synthesis in vitro using rat and mouse hepatocytes. IL-1 caused significant increased synthesis of alpha 1-acid glycoprotein and smaller increases in the synthesis of other acute-phase proteins, and significant decreased synthesis of albumin. The pattern of induction of acute-phase proteins differs from that seen with a separate 30,000 molecular weight hepatocyte-stimulating factor from human monocytes described previously. We conclude that human IL-1 is one of the mediators responsible for the acute-phase protein response of the liver in inflammation and can directly cause stimulation of specific gene expression in normal hepatocytes. |