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, Th ey are able to influence the function of other liver cells, i.e. sinus oidal endothelial cells, Ito cells and hepatocytes, The three known ma jor functions of Kupffer cells are clearance of endotoxin from the por tal circulation, release of soluble mediators and presentation of anti gen. Methods: Human Kupffer cells were isolated by collagenase perfusi on followed by centrifugal elutriation and analyzed for cytokine secre tion after 3 days in culture. Results: We found that freshly isolated human Kupffer cells secreted the anti-inflammatory cytokine interleuki n-10 in response to stimulation with lipopolysaccharide, The release o f interleukin-10 was maximal 12-24 h after lipopolysaccharide challeng e, Furthermore, we could show that exogenous interleukin-10 downregula ted the release of the proinflammatory cytokines interleukin-6 and tum or necrosis factor a by Kupffer cells after lipopolysaccharide stimula tion, The release of interleukin-6 was maximal 24 h after stimulation and interleukin-10 inhibited interleukin-6 release after 6 h. Tumor ne crosis factor a showed maximal secretion 6 h after stimulation and exo genous interleukin-10 also downregulated the tumor necrosis factor a r elease after 6 h. Conclusions: Kupffer cells are exposed physioliogica lly to lipopolysaccharide present in portal venous blood, Given the kn own anti-inflammatory effect of interleukin-10, our findings of secret ion of interleukin-10 by Kupffer cells in response to lipopolysacchari de and suppression of interleukin-6 and tumor necrosis factor a releas e by Kupffer cells in vitro through exogenous interleukin-10 suggest a n important role for interleukin-10 in the regulation of the local imm une response in the liver sinusoid.