Modulation of hepatocyte protein synthesis by endotoxin-activated Kupffer cells. III. Evidence for the role of a monokine similar to but not identical with interleukin-1

G. A KELLER; M. A WEST; J. T HARTY; L. A WILKES; F. B CERRA; R. L SIMMONS

doi:10.1097/00000658-198504000-00006

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Modulation of hepatocyte protein synthesis by endotoxin-activated Kupffer cells. III. Evidence for the role of a monokine similar to but not identical with interleukin-1

Journal article

Peer reviewed

Modulation of hepatocyte protein synthesis by endotoxin-activated Kupffer cells. III. Evidence for the role of a monokine similar to but not identical with interleukin-1

G. A KELLER, M. A WEST, J. T HARTY, L. A WILKES, F. B CERRA and R. L SIMMONS

Annals of surgery, Vol.201(4), pp.436-443

1985

DOI: 10.1097/00000658-198504000-00006

PMID: 3883925

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Abstract

The authors previously reported that unstimulated peritoneal macrophages and LPS stimulated Kupffer cell-rich nonparenchymal liver cells (NPC) can inhibit protein synthesis in cultured rat hepatocytes. Hepatocyte function was similarly altered by supernatants from LPS-triggered NPC. Secretory products of macrophages and Kupffer cells (monokines) are possible mediators in this model of cell-mediated modulation of hepatocyte function. In this article, supernatants from NPC capable of altering hepatocyte protein synthesis were found to contain significant amounts of one monokine, interleukin-1 (IL-1). The kinetics of the generation of the ability to inhibit protein synthesis and the appearance of IL-1 activity were roughly parallel for the first 24 hours. Exposure of hepatocytes to NPC supernatant and commercially available highly purified IL-1 resulted in similar response patterns with regard to onset of inhibition and progression of suppression after removal. Certain discrepancies cast doubt, however, on the likelihood that IL-1 is the mediator in this model of cell-mediated inhibition of hepatocyte protein synthesis. Commercial human IL-1 preparations did not always suppress protein synthesis in cultured rat hepatocytes. Furthermore, IL-1 activity was stable for several days but hepatocyte inhibition was lost. Unstimulated peritoneal macrophage supernatants containing IL-1 activity could not inhibit protein synthesis in hepatocytes. The evidence supports the idea that appropriately stimulated cells of monocyte-macrophage lineage (including Kupffer cells that lie in direct apposition to hepatocytes) could mediate hepatocyte malfunction by means of secreted monokines similar to, but not necessarily identical to, IL-1.

Biological and medical sciences

Intensive care medicine

Medical sciences

Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy

Emergency and intensive care: digestive diseases. Bioartificial liver

Details

Title: Subtitle: Modulation of hepatocyte protein synthesis by endotoxin-activated Kupffer cells. III. Evidence for the role of a monokine similar to but not identical with interleukin-1
Creators: G. A KELLER - Univ. Minnesota, veterans Foreign Wars cancer res. center, Minnesota MN 55455, United States
M. A WEST - Univ. Minnesota, veterans Foreign Wars cancer res. center, Minnesota MN 55455, United States
J. T HARTY - Univ. Minnesota, veterans Foreign Wars cancer res. center, Minnesota MN 55455, United States
L. A WILKES - Univ. Minnesota, veterans Foreign Wars cancer res. center, Minnesota MN 55455, United States
F. B CERRA - Univ. Minnesota, veterans Foreign Wars cancer res. center, Minnesota MN 55455, United States
R. L SIMMONS - Univ. Minnesota, veterans Foreign Wars cancer res. center, Minnesota MN 55455, United States
Resource Type: Journal article
Publication Details: Annals of surgery, Vol.201(4), pp.436-443
DOI: 10.1097/00000658-198504000-00006
PMID: 3883925
NLM abbreviation: Ann Surg
ISSN: 0003-4932
eISSN: 1528-1140
Publisher: Lippincott; Hagerstown, MD
Language: English
Date published: 1985
Academic Unit: Pathology
Record Identifier: 9984047632902771

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