Autoregulatory effect of interleukin-10 on proinflammatory cytokine production by Porphyromonas gingivalis lipopolysaccharide-tolerant human monocytes

Hidetoshi Shimauchi, Tomohiko Ogawa, Kozo Okuda, Yutaka Kusumoto, Hirohi Okada

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Pretreatment of human peripheral blood monocytes with a very low concentration (0.1 ng/ml) of Porphyromonas gingivalis lipopolysaccharides (LPS) resulted in a significant decrease of interleukin-6 (IL-6) production, but not IL-8 production, by restimulation of a high concentration (1 μg/ml) of the same LPS. In contrast, the same pretreatment with Escherichia coli LPS resulted in the enhanced production of both IL-6 and IL-8 after restimulation. The selective induction by P. gingivalis LPS tolerance of IL- 6 production developed in a time-dependent manner during the primary culture. P. gingivalis LPS-pretreated cells were also refractory to a high-dose E. coli LPS restimulation in terms of IL-6 production. The expression of IL-6 mRNA decreased 10 h after restimulation of P. gingivalis LPS-pretreated monocytes. Furthermore, an up-regulation of anti-inflammatory cytokine IL-10 upon a second high-dose LPS rechallenge occurred at the same time point in the pretreated cells. We studied the role of IL-10 in the process of IL-6 down-regulation. Neutralization by an anti-IL-10 polyclonal antibody prevented IL-6 down-regulation in P. gingivalis LPS-pretreated monocytes, whereas IL-8 production was not affected. Addition of exogenous IL-10 during the high-dose LPS stimulation of untreated cells substituted for the LPS pretreatment and resulted in the inhibition of IL-6 production in a dose- dependent manner. A higher dose of IL-10 was required to suppress IL-8 synthesis from monocytes. Our data suggest that IL-10 mediates IL-6 down- regulation in P, gingivalis LPS-tolerant monocytes in an autocrine manner.

Original languageEnglish
Pages (from-to)2153-2159
Number of pages7
JournalInfection and immunity
Volume67
Issue number5
Publication statusPublished - 1999 May 1

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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