Characterization of interleukin-1 and interleukin-6 production by hepatic endothelial cells and macrophages

Interleukin‐1 (EL‐1) and interleukin‐6 (IL‐6) derived from Kupffer cells are major inducers of hepatic inflammation and the acute phase response. The present studies demonstrate that liver endothelial cells also produce significant quantities of IL‐1 and IL‐6, suggesting that these cells also partic...

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Bibliographic Details
Published in:Journal of leukocyte biology 1993-02, Vol.53 (2), p.126-132
Main Authors: Feder, Lisa S., Todaro, Jeanine A., Laskin, Debra L.
Format: Article
Language:English
Subjects:
acute phase response
Analysis of the immune response. Humoral and cellular immunity
Animals
Biological and medical sciences
Cells, Cultured
cytokine
Endothelium - drug effects
Endothelium - physiology
Escherichia coli
Female
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Immunobiology
Interleukin-1 - biosynthesis
Interleukin-6 - biosynthesis
Kinetics
Kupffer Cells - drug effects
Kupffer Cells - physiology
Lipopolysaccharides - pharmacology
liver
Liver - enzymology
Lymphokines, interleukins ( function, expression)
Rats
Rats, Sprague-Dawley
Regulatory factors and their cellular receptors
Time Factors
Upopolysaccharide
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Summary:Interleukin‐1 (EL‐1) and interleukin‐6 (IL‐6) derived from Kupffer cells are major inducers of hepatic inflammation and the acute phase response. The present studies demonstrate that liver endothelial cells also produce significant quantities of IL‐1 and IL‐6, suggesting that these cells also participate in these processes. Endothelial cells and macrophages were isolated from female Sprague‐Dawley rats by combined collagenase and pronase perfusion of the liver followed by centrifugal elutriation. In the absence of stimulation, endothelial cells were found to spontaneously produce IL‐1 and IL‐6 in a time‐dependent manner, reaching maximal levels after 10 h in culture for IL‐1 and 6‐8 h for EL‐6. The amount and kinetics of cytokine production by hepatic endothelial cells were similar to those observed with Kupffer cells. In further studies, the effects of lipo‐ polysaccharide (LPS), a potent liver macrophage activator and inflammatory agent, on cytokine release were analyzed. Treatment of rats with LPS resulted in a decrease in IL‐1 release by both cell types compared to cells from untreated animals. In contrast, LPS treatment had no major effect on IL‐6 release. We also found that both macrophages and endothelial cells could be induced to produce additional IL‐1 and IL‐6 by treatment with LPS in vitro, but only if they were preincubated for at least 24 h prior to stimulation with LPS and analyzed for cytokine release. These data demonstrate that liver endothelial cells, like Kupffer cells, have the capacity to produce immunoregulatory and proinfiammatory cytokines.
ISSN:0741-5400
1938-3673
DOI:10.1002/jlb.53.2.126