Characterization of interleukin-1 and interleukin-6 production by hepatic endothelial cells and macrophages.
Interleukin-1 (IL-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 IL-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 lipopolysaccharide (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 proinflammatory cytokines.
Feder
L S
LS
Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey 08855-0789.
Todaro
J A
JA
Laskin
D L
DL
D000818:Animals; D002478:Cells, Cultured; D004727:Endothelium / Q000187:drug effects / Q000502:physiology*; D004926:Escherichia coli; D005260:Female; D007375:Interleukin-1 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D007700:Kinetics; D007728:Kupffer Cells / Q000187:drug effects / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides