Anti-inflammatory Effects of Sodium Butyrate on Human Monocytes: Potent Inhibition of IL-12 and Up-Regulation of IL-10 Production

FASEB J. 2000 Dec;14(15):2380-2. doi: 10.1096/fj.00-0359fje.

Abstract

Cytokines are critical in regulating unresponsiveness versus immunity towards enteric antigens derived from the intestinal flora and ingested food. There is increasing evidence that butyrate, a major metabolite of intestinal bacteria and crucial energy source for gut epithelial cells, also possesses anti-inflammatory properties. Its influence on cytokine production, however, is not established. Here, we report that butyrate strongly inhibits interleukin-12 (IL-12) production by suppression of both IL-12p35 and IL-12p40 mRNA accumulation, but massively enhances IL-10 secretion in Staphylococcus aureus cell-stimulated human monocytes. The effect of butyrate on IL-12 production was irreversible upon the addition of neutralizing antibodies to IL-10 or transforming growth factor b1 and of indomethacin. In anti-CD3-stimulated peripheral blood mononuclear cells, butyrate enhanced IL-10 and IL-4 secretion but reduced the release of IL-2 and interferon-g. The latter effect was in part a result of suppressed IL-12 production but also a result of inhibition of IL-12 receptor expression on T cells. These data demonstrate a novel anti-inflammatory property of butyrate that may have broad implications for the regulation of immune responses in vivo and could be exploited as new therapeutic approach in inflammatory conditions.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Butyrates / pharmacology*
  • Cytokines / biosynthesis
  • Dose-Response Relationship, Drug
  • Humans
  • Interleukin-10 / biosynthesis*
  • Interleukin-12 / biosynthesis*
  • Models, Immunological
  • Monocytes / drug effects*
  • Receptors, Interleukin / biosynthesis
  • Receptors, Interleukin-12

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Butyrates
  • Cytokines
  • Receptors, Interleukin
  • Receptors, Interleukin-12
  • Interleukin-10
  • Interleukin-12