Open AccessRegulation of endotoxin‐induced IL‐6 production in liver sinusoidal endothelial cells and Kupffer cells by IL‐10
Author(s) -
KNOLLE P. A.,
LO¨SER E.,
PROTZER U.,
DUCHMANN R.,
SCHMITT E.,
ZUM BU¨SCHENFELDE K.H. M.,
ROSEJOHN S.,
GERKEN G.
Publication year - 1997
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1046/j.1365-2249.1997.d01-959.x
Subject(s) - kupffer cell , cytokine , inflammation , secretion , biology , proinflammatory cytokine , immunology , endothelial stem cell , interleukin 8 , endocrinology , in vitro , biochemistry
Sinusoidal endothelial cells and Kupffer cells are the first cell populations in the liver that come into contact with gut‐derived endotoxin in portal blood. Although endotoxin concentrations as high as 1 ng/ml are physiologically present in portal blood, no local inflammation is seen. We show that the proinflammatory cytokine IL‐6, which is central to the development of inflammatory reactions in the liver, is produced by sinusoidal endothelial cells and Kupffer cells in response to low concentrations of endotoxin (100 pg/ml to 1 ng/ml). The anti‐inflammatory cytokine IL‐10 down‐regulated endotoxin‐induced IL‐6 release in endothelial and Kupffer cells. Importantly, Kupffer cells secreted IL‐10 after endotoxin stimulation and may therefore participate in the local regulation of inflammation. We have found that IL‐6 secretion in Kupffer cells is tightly regulated by endogenous IL‐10, because increased IL‐6 secretion resulted when neutralizing antibodies to IL‐10 were added to resting and endotoxin‐challenged Kupffer cells. Furthermore, repeated exposure of endothelial cells to endotoxin induced a state of tolerance which resulted in decreased release of IL‐6 in response to a second endotoxin challenge. Our results support the notion that inflammatory reactions in the liver in response to endotoxin are down‐regulated by local release of the anti‐inflammatory cytokine IL‐10 that is produced by Kupffer cells.