STIMULATION OF CHICK HEPATOCYTE FIBRONECTIN PRODUCTION BY FIBROBLAST-CONDITIONED MEDIUM IS DUE TO INTERLEUKIN-6

Interleukin-6 (IL6) is produced by different cell types, including mon ocytes and fibroblasts. We show that recombinant human IL6 (rhIL6) and chick fibroblast conditioned medium stimulate plasma fibronectin (PFn ) and PFn mRNA production by cultured chick hepatocytes in a dose-depe ndent manner. Lipopolysaccharide (LPS) treatment of fibroblast culture s induces higher levels of the PFn stimulating activity. These effects are blocked by preincubation of either rhIL6 or LPS-stimulated chick fibroblast conditioned medium with anti-rhIL6 antibody before treatmen t of hepatocytes, indicating that the conditioned medium contains chic k fibroblast-derived IL-6 (cfIL6). Further, LPS induces fibroblast pro duction of a proportional increase in cfIL6 detectable by a human IL6 ELISA. cfIL6 maximally stimulates chick hepatocyte PFn production by 2 4 h (4.5-fold). Dexamethasone acts more rapidly, but maximal stimulati on is only 2.3-fold. Hepatocyte Fn mRNA levels are even more substanti ally stimulated by dexamethasone and cfIL6 (up to 8.9- and 18.5-fold b y 12 h, declining to 2.3 and 4.2-fold by 24 h, respectively). The effe ct cfIL6 with or without dexamethasone on hepatocyte PFn levels are co mparable. These observations are consistent with the role of IL6 as a major mediator of acute phase protein production.