HUMAN KUPFFER CELLS SECRETE IL-10 IN RESPONSE TO LIPOPOLYSACCHARIDE (LPS) CHALLENGE

Background/Aims: Kupffer cells are involved in local immunoregulation in the liver by secretion of cytokines and direct cellular contact, They are able to influence the function of other liver cells, i.e. sinusoidal endothelial cells, Ito cells and hepatocytes, The three known major functions of Kupffer cells are clearance of endotoxin from the portal circulation, release of soluble mediators and presentation of antigen. Methods: Human Kupffer cells were isolated by collagenase perfusion followed by centrifugal elutriation and analyzed for cytokine secretion after 3 days in culture. Results: We found that freshly isolated human Kupffer cells secreted the anti-inflammatory cytokine interleukin-10 in response to stimulation with lipopolysaccharide, The release of interleukin-10 was maximal 12-24 h after lipopolysaccharide challenge, Furthermore, we could show that exogenous interleukin-10 downregulated the release of the proinflammatory cytokines interleukin-6 and tumor necrosis factor a by Kupffer cells after lipopolysaccharide stimulation, The release of interleukin-6 was maximal 24 h after stimulation and interleukin-10 inhibited interleukin-6 release after 6 h. Tumor necrosis factor a showed maximal secretion 6 h after stimulation and exogenous interleukin-10 also downregulated the tumor necrosis factor a release after 6 h. Conclusions: Kupffer cells are exposed physioliogically to lipopolysaccharide present in portal venous blood, Given the known anti-inflammatory effect of interleukin-10, our findings of secretion of interleukin-10 by Kupffer cells in response to lipopolysaccharide and suppression of interleukin-6 and tumor necrosis factor a release by Kupffer cells in vitro through exogenous interleukin-10 suggest an important role for interleukin-10 in the regulation of the local immune response in the liver sinusoid.