Porphyromonas gingivalis LPSによるトレランスの誘導

Lipopolysaccharide (LPS) tolerance, a hyporesponsive state to endotoxin or LPS stimulation, was induced in human monocytes by pretreatment of monocytes to a very low dose of Porphyromonas gingivalis LPS. Interleukin (IL) -6 production, but not IL-8 production, in response to LPS restimulation was significantly suppressed. The same pretreatment resulted in up regulation of superoxide (O2) production. The selective induction of P. gingivalis LPS tolerance on IL-6 production developed in a time dependent manner during the primary culture without decrease of CD14 expression on cell surface. The expression of IL-6 mRNA decreased 10 h after restimulation of P. gingivalis LPS-pretreated monocytes. An up-regulation of IL 10 upon a second high dose LPS rechallenge occurred at the same time-point in the pretreated cells. Neutralization by an anti-IL-10 polyclonal antibody prevented IL-6 downregulation in P. gingivalis LPS-pretreated monocytes, whereas IL-8 production was not affected. These data suggest that tolerance of human monocytes to P. gingivalis LPS seems to be a state of differential deactivation in which some functions are impaired whereas others are retained or enhanced. Furthermore, autocrine IL-10 is essential for IL-6 downregulation in P. gingivalis LPS-tolerant monocytes.