Regulation of microglial inflammatory response by sodium butyrate and short-chain fatty acids

Br J Pharmacol. 2004 Mar;141(5):874-80. doi: 10.1038/sj.bjp.0705682. Epub 2004 Jan 26.


1. Recent studies have shown that sodium butyrate and other short-chain fatty acids (SCFAs) can prevent inflammation in colon diseases. Our aim was to elucidate whether sodium butyrate and SCFAs regulate the inflammatory responses in different neural inflammation models in cell cultures. 2. Inflammatory responses to LPS-induced microglial activation were recorded by the secretion of nitric oxide (NO) and cytokines IL-6 and TNF-alpha and related to the changes in the DNA-binding activities of NF-kappaB complex. 3. We observed that sodium butyrate is strongly anti-inflammatory against LPS-induced responses in rat primary microglia as well as in hippocampal slice cultures and in neural cocultures of microglial cells, astrocytes and cerebellar granule neurons. 4. In murine N9 microglial cell line, instead, sodium butyrate and other SCFAs (propionate, valerate and caproate) enhanced the LPS-induced inflammatory response. 5. The pretreatment with butyrate before LPS exposure induced an equal or more enhanced response than simultaneous exposure with butyrate and LPS. This indicates that butyrate induces an adaptative response against microglial activation. 6. We also observed that butyrate treatment both in transformed N9 cells and in hippocampal slice cultures downregulates the NF-kappaB-binding capacity induced by LPS stimulation. 7. Our results show that butyrate is anti-inflammatory in primary, brain-derived microglial cells, as observed recently in colon diseases, but proinflammatory in transformed, proliferating N9 microglial cells, which may be related to the anticancer properties of butyrate observed in tumor cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Butyrates / pharmacology*
  • Cell Line
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Fatty Acids / metabolism*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Microglia / drug effects*
  • Microglia / metabolism
  • Microglia / pathology*
  • Rats
  • Rats, Wistar


  • Butyrates
  • Cytokines
  • Fatty Acids