An age-related decline in interleukin-10 may contribute to the increased expression of interleukin-6 in brain of aged mice

Shi Ming Ye, Rodney W Johnson

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: The DNA-binding activity of nuclear factor κB (NFκB) is elevated in brain of aged mice, resulting in elevated levels of the inflammatory cytokine interleukin (IL)-6. The purpose of this study was to determine if in the brain of aged mice a decrease in the anti-inflammatory cytokine IL-10 contributes to the increase in IL-6. Methods: In initial studies coronal brain sections and glial cells from adult (6-months-old) and aged (24-months-old) mice were incubated in the presence or absence of lipo-polysaccharide (LPS) and the concentrations of IL-6 and IL-10 in supernatants were determined. In subsequent studies, the effect of recombinant murine IL-10 on constitutive and inducible NFκB activity, IL-6 mRNA expression and IL-6 protein secretion by glia cultured from brains of adult and aged mice was determined. Results: Coronal brain sections and glia from aged mice secreted more IL-6 and less IL-10 than brain sections and glia from adults. This effect of age was evident in the absence and presence of LPS and suggested that a decrease in IL-10 production permitted increased IL-6 production. Consistent with this idea, treatment of glia from aged mice with recombinant IL-10 decreased both constitutive and inducible binding of NFκB to the IL-6 gene promoter. The decrease in NFκB activity was associated with a reduction of IL-6 mRNA and protein. Exogenous IL-10, however, had no effect on NFκB activity, which was undetectable in unstimulated glia from adult mice, and did not decrease steady-state levels of IL-6 mRNA or IL-6 protein secretion. Conclusions: Collectively, these studies suggest that IL-10 constrained IL-6 gene expression in the adult brain, but in the aged brain it decreased and thus enabled a cascade of intracellular events that increased expression of the IL-6 gene.

Original languageEnglish (US)
Pages (from-to)183-192
Number of pages10
JournalNeuroImmunoModulation
Volume9
Issue number4
DOIs
StatePublished - Dec 1 2001

Keywords

  • Aging
  • Brain
  • Cytokines
  • Interleukin-10
  • Interleukin-6

ASJC Scopus subject areas

  • Immunology
  • Endocrinology
  • Neurology
  • Endocrine and Autonomic Systems

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