title: Interleukin-8 can mediate acute-phase protein production by isolated human hepatocytes.
abstract: During the course of studies designed to identify the role of cytokines in the reprioritization of hepatic protein synthesis associated with cachexia we detected a hepatocyte-stimulating moiety in the supernatants of pancreatic cancer cells that was unrelated to interleukin (IL)-6. This study identifies that moiety as IL-8 and investigates the role of IL-8 in the induction of acute-phase protein production. The human pancreatic cancer cell line MIA PaCa-2 produced >1 ng/ml of IL-8 per 24 h, and supernatants from this cell line induced C-reactive protein (CRP) production from isolated human hepatocytes. Addition of neutralizing anti-human IL-8 antibody to such supernatants produced almost complete inhibition of CRP production. The addition of recombinant human IL-8 to hepatocytes resulted in a dose-dependent increase in CRP, alpha1-acid glycoprotein, and alpha1-antichymotrypsin production and a decrease in the production of transferrin and prealbumin. This study demonstrates that recombinant or tumor-derived IL-8 can modulate acute-phase protein production from isolated human hepatocytes and from human hepatoma cells.
authors.affiliation: University Department of Surgery, Royal Infirmary of Edinburgh, United Kingdom.
authors.forename: S J
authors.initials: SJ
authors.lastname: Wigmore
authors.forename: K C
authors.initials: KC
authors.lastname: Fearon
authors.forename: J P
authors.initials: JP
authors.lastname: Maingay
authors.forename: P B
authors.initials: PB
authors.lastname: Lai
authors.forename: J A
authors.initials: JA
authors.lastname: Ross
mesh_terms: D000209:Acute-Phase Proteins / Q000096:biosynthesis*; D002097:C-Reactive Protein / Q000096:biosynthesis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D016209:Interleukin-8 / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism; D009961:Orosomucoid / Q000096:biosynthesis; D010190:Pancreatic Neoplasms / Q000276:immunology; D016133:Polymerase Chain Reaction; D011228:Prealbumin / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D014168:Transferrin / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D000514:alpha 1-Antichymotrypsin / Q000096:biosynthesis
chemical_list: D000209:Acute-Phase Proteins; D017077:Culture Media, Conditioned; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D009961:Orosomucoid; D011228:Prealbumin; D011994:Recombinant Proteins; D014168:Transferrin; D000514:alpha 1-Antichymotrypsin; D002097:C-Reactive Protein