KUPFFER CELL- MEDIATED CYTOTOXICITY INDUCED BY LIPOPOLYSACCHARIDE0111:B4 IS GREATER IN DOGS THAN IN RATS AND MONKEYS

To clarify the mechanism of sensitivity to an endotoxin lipopolysaccharide LPS0111:B4, which causes severe liver injury in a variety of animals, we have developed an in vitro assay to measure Kupffer cell-mediated cytotoxicity in the human liver cell line, WRL68. This assay could detect the decrease in Kupffer cell activity induced by gadolinium chloride (GdCl 3 ), which is an inhibitor in Kupffer cells. Among Kupffer cells derived from dogs, rats, and monkeys, LPS-activated canine Kupffer cells exhibited remarkably high cytotoxicity against WRL68 cells. This species difference is correlated with a species difference in the lethality of LPS0111:B4. Additionally, the conditioned medium of LPS-activated canine Kupffer cells was also cytotoxic to WRL68 cells. To identify the mediators of this cytotoxicity, we measured the accelerated release of interleukin-1β, and interleukin-6 from Kupffer cells on stimulation with LPS0111:B4. From the correlation of the response to LPS0111:B4, interleukin-1β and interleukin-6 are considered to be responsible for the canine Kupffer cell-mediated cytotoxicity of LPS0111:B4.