Interleukin-1β inhibits lipopolysaccharide-lnduced tumor necrosis factor and interleukin-1β production in the brain without affecting the activation of the hypothalamus-pituitary-adrenal axis

Elena di Santo, Marina Sironi, Pietro Pozzi, Paola Gnocchi, Anna Maria Isetta, Anne Delvaux, Michel Goldman, Arnaud Marchant, Pietro Ghezzi

Research output: Contribution to journalArticlepeer-review

Abstract

Interleukin (IL) 10 inhibits endotoxin (lipopolysaccharide; LPS) induced tumor necrosis faclor (TNF) production in vivo and in vitro. In turn. IL-10 is induced by LPS and acts as a negative feedback to limit TNF production. We investigated the effects of IL-10 on brain TNF and IL-βp production induced by a central LPS administration in mice. Because central LPS also induces peripheral TNF. we also measured the serum TNF levels. A single intracere-broventricular injection of murine recombinant IL-10 (75 μg/mouse) simultaneously with LPS (2.5 μg/mouse) almost completely inhibited brain TNF production. The brain IL-β production was also inhibited, as was the serum concentration of the acute-phase protein serum amyloid A. On the other hand, intracerebroventricular administration of an anti-IL-10 monoclonal antibody (JES5-2A5; 60 μg/mouse) potentiated brain TNF and IL-β production. Identical results were obtained when the serum TNF levels were measured. IL-10 did not affect the LPS-induced increase of serum corticosterone. the main endogenous inhibitor of TNF production, or the induction of IL-6. These results indicate that LPS-induced IL-10 can act as an important endogenous inhibitor of brain TNF production and suggest an anti-inflammatory role for IL-10 in the central nervous system.

Original languageEnglish
Pages (from-to)149-154
Number of pages6
JournalNeuroImmunoModulation
Volume2
Issue number3
DOIs
Publication statusPublished - 1995

Keywords

  • Endotoxin
  • Hypothalamus-pituitary-adrenal axis
  • Interleukin 1
  • Interleukin 10
  • Serum amyloid A
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Endocrinology
  • Immunology
  • Endocrine and Autonomic Systems
  • Neurology
  • Neuroscience(all)

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