Role of cytokines and growth factors in the induced synthesis of proteinase inhibitors belonging to acute phase proteins.

The effects of various cytokines on synthesis and secretion of albumin and some proteinase inhibitors belonging to the class of macroglobulins, serpins and cysteine proteinase inhibitors were studied in the primary cultures of rat and mouse hepatocytes and established human hepatoma cell line Hep G2. In all tested systems interleukin 6 depressed the synthesis of albumin and enhanced the synthesis of antichymotrypsin (or contrapsin) and alpha-1-proteinase inhibitor, while in the rat alpha-2-macroglobulin and T-kininogen (thiostatin) were the major acute phase reactants. Smaller and variable effects were observed with interleukin-1, tumour necrosis factor, interferon-gamma, transforming growth factor-beta and epidermal growth factor. Searching for the feed-back regulatory mechanism responsible for induced synthesis of proteinase inhibitors we found that cultured human lung fibroblasts exposed to human alpha-1-antichymotrypsin or antichymotrypsin-cathepsin G complexes produce significantly more interleukin 6 which stimulates Hep G2 cells to augmented synthesis of several acute phase proteins.