Short-chain fatty acids (SCFAs) with the anti-inflammatory capacity are produced by intestinal bacteria; however, their effect on the acute systematical
inflammation remains unclear. This study aimed to investigate the effects of SCFAs,
acetate,
propionate and
butyrate, on
septic shock and the underlying mechanism. The LPS-induced septic model was used to evaluate the function of SCFAs by survival rate observation. Only
butyrate, but not
acetate or
propionate, significantly decrease the mortality of septic mice. At 2 h and 6 h of LPS administration, the levels of TNF-α,
IL-6 and IL-1β in plasma were measured by ELISA to estimate the effects of
butyrate pretreatment on excessive
inflammation. And the anti-inflammatory mediators including TGF-β,
IL-10 and LXT4 in plasma were detected for further mechanism study in septic mice. Moreover, the murine macrophage-like RAW 264.7 cells were stimulated by LPS to further confirm the finding in vivo. Pretreatment with
butyrate led to significant attenuation of the LPS-induced elevation of TNF-α,
IL-6 and IL-1β levels. However, when detecting the anti-inflammatory factors, a significant increase in
IL-10, but not TGF-β or LXT4, was shown in
butyrate-pretreated group. Pretreatment of RAW 264.7 cells with
butyrate led to downregulation of LPS-induced pro-inflammatory mediators,
IL-6 and IL-1β, but did not affect the level of TNF-α, and increased
IL-10 (P < 0.01). In conclusion, SCFA
butyrate significantly attenuated the
inflammation against
sepsis through upregulation of anti-inflammatory
IL-10.