Anti-inflammatory effects of sodium butyrate on human monocytes: potent inhibition of IL-12 and up-regulation of IL-10 production.
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.
Säemann
M D
MD
Institute of Immunology, University of Vienna, Austria.
Böhmig
G A
GA
Osterreicher
C H
CH
Burtscher
H
H
Parolini
O
O
Diakos
C
C
Stöckl
J
J
Hörl
W H
WH
Zlabinger
G J
GJ
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002087:Butyrates / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis*; D018448:Models, Immunological; D009000:Monocytes / Q000187:drug effects*; D018123:Receptors, Interleukin / Q000096:biosynthesis; D053707:Receptors, Interleukin-12
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002087:Butyrates; D016207:Cytokines; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D016753:Interleukin-10; D018664:Interleukin-12