title: Endotoxin stimulates interleukin-6 production by human Kupffer cells.
abstract: Interleukin-6 (IL-6) induces acute-phase protein synthesis in human hepatocytes. We evaluated whether the contiguous hepatic macrophages, human Kupffer cells (HKC), produce IL-6 in response to an inflammatory stimulus. HKC were harvested from collagenase-digested normal liver biopsies and purified (greater than 95% by phagocytosis) by adherence. Following overnight culture, 5 x 10(5) HKC were repleted with fresh media with or without 2.5 micrograms/ml of endotoxin (LPS). Parallel cultures contained polymyxin-B (10 micrograms/ml) or antihuman-IL-6 antibody (4 units/ml). Timed supernatants were collected and IL-6 levels (ng/ml) measured (B9.9 proliferative bioassay). Data analysis was by the paired Student's t test. Unstimulated HKC produced negligible IL-6 levels (less than 0.150 ng/ml). Endotoxin invoked early and sustained HKC production of IL-6, which was completely (P less than 0.001) abrogated by the addition of the anti-IL-6 antibody. Polymyxin B, an LPS-inhibitor, also blocked (P less than 0.001) IL-6 production, indicating the specificity of the response to the inflammatory stimulus. This is the first evidence that HKC can produce IL-6 in response to LPS. Local intrahepatic production of IL-6 may provide a necessary paracrine signal for HKC to amplify directly neighboring hepatocyte acute-phase responses during inflammation in man.
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: M P
authors.initials: MP
authors.lastname: Callery
authors.forename: T
authors.initials: T
authors.lastname: Kamei
authors.forename: M W
authors.initials: MW
authors.lastname: Flye
mesh_terms: D002478:Cells, Cultured / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D007728:Kupffer Cells / Q000187:drug effects* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides