Effects of cytokine antagonists on the hepatic acute-phase response

The Journal of Surgical Research
J E MazuskiM J Shapiro

Abstract

Endotoxin-induced hepatic acute-phase protein synthesis has been thought to be primarily regulated through cytokines such as interleukin-1 (IL-1) and interleukin-6 (IL-6). Previously, it was found that a 23-kDa murine acute-phase protein, the lipopolysaccharide (LPS)-induced protein (LIP), was synthesized following treatment of hepatocytes in vitro with LPS. Since this protein was also induced by IL-1 and IL-6, the present studies were undertaken to determine if the effect of endotoxin was mediated through these cytokines. Primary cultures of murine hepatocytes were treated with LPS, IL-1, IL-6, or an LPS-stimulated macrophage supernatant in the presence or absence of the IL-1 receptor antagonist (IL-1 RA) and/or an anti-IL-6 antibody. The cells were then radiolabeled with [35S]methionine. LIP was detected by electrophoresis and autoradiography of the secreted proteins. In vitro, IL-1 RA completely inhibited the stimulation of LIP synthesis elicited by IL-1 and the macrophage supernatant, but did not affect LPS-stimulated synthesis of this protein. The anti-IL-6 antibody inhibited IL-6-triggered synthesis of LIP, but had no effect on LPS-stimulated synthesis. Hepatocytes isolated from mice treated in vivo with both IL-1 RA and ...Continue Reading

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Citations

Aug 26, 2006·Veterinary Immunology and Immunopathology·T R Scott, H S Lillehoj
Oct 12, 2000·The Journal of Surgical Research·R N CooneyT C Vary
Jan 25, 2000·The Journal of Surgical Research·E M GrossmannJ E Mazuski
Mar 21, 2002·Critical Care Medicine·Robert N Cooney, Gladys Yumet
Nov 24, 1999·Current Opinion in Clinical Nutrition and Metabolic Care·J M Argilés, F J López-Soriano
Oct 2, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ramiro JoverJosé V Castell
Oct 6, 1998·The Journal of Surgical Research·J E MazuskiW E Longo
Jul 29, 1999·The Journal of Surgical Research·N PanesarJ E Mazuski

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