DIFFERENT EFFICACY OF SOLUBLE CD14 TREATMENT IN HIGH-DOSE AND LOW-DOSE LPS MODELS

Background About 50% of septic shock cases are attributed to Gram-nega tive bacteria or their cell wall compound lipopolysaccharide (LPS, end otoxin). An attractive therapeutic strategy could target the binding o f LPS to its cellular receptors. In vitro the soluble form of the endo toxin receptor CD14 (sCD14) competitively prevents binding of LPS to m embrane-bound CD14 and inhibits LPS-stimulated macrophage responses. M ethods We tested the in vivo endotoxin-neutralizing capacity of human recombinant sCD14 using a mouse model of shock induced by 8 mu g g(-1) of LPS from Salmonella abortus equi. Results In this model, treatment with sCD14 reduced mortality if administered before or simultaneously with LPS. However, application of sCD14 had no effect on the secretio n of early proinflammatory cytokines and did not protect the animals a gainst the development of apparent shock symptoms and liver injury. sC D14 also failed to prevent LPS-inducible (7.5 ng g(-1)) liver injury i n galactosamine-sensitized mice. Conclusion In line with these finding s, sCD14 did not block LPS-induced activation of Kupffer cells in vitr o, which might explain why the compound only partially protected in vi vo.