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Short-Chain Fatty Acids Induce Pro-Inflammatory Cytokine Production Alone and in Combination with Toll-Like Receptor Ligands


Gregory T. Spear, Department of Immunology/Microbiology, Rush University Medical Center, 1735 W. Harrison Street, Chicago, IL 60612, USA. E-mail:


Citation Mirmonsef P, Zariffard MR, Gilbert D, Makinde H, Landay, AL, Spear GT. Short-chain fatty acids induce pro-inflammatory cytokine production alone and in combination with Toll-like receptor ligands. Am J Reprod Immunol 2012; 67: 391–400

Problem  Short-chain fatty acids (SCFAs), produced at relatively high levels by anaerobic bacteria in bacterial vaginosis (BV), are believed to be anti-inflammatory. BV, a common alteration in the genital microbiota associated with increased susceptibility to HIV infection, is characterized by increased levels of both pro-inflammatory cytokines and SCFAs. We investigated how SCFAs alone or together with Toll-like receptor (TLR) ligands affected pro-inflammatory cytokine secretion.

Method of study  Cytokines were measured by ELISA. Flow was used for phenotyping and reactive oxygen species (ROS) measurement.

Results  Short-chain fatty acids, at 20 mm, induced interleukin (IL)-8, IL-6, and IL-1β release, while lower levels (0.02–2 mm) did not induce cytokine secretion. Levels >20 mm were toxic to cells. Interestingly, lower levels of SCFAs significantly enhanced TLR2 ligand- and TLR7 ligand-induced production of IL-8 and TNFα in a time- and dose-dependent manner, but had little effect on lipopolysaccharide-induced cytokine release. SCFAs mediated their effects on pro-inflammatory cytokine production at least in part by inducing the generation of ROS.

Conclusion  Our data suggest that SCFAs, especially when combined with specific TLR ligands, contribute to a pro-inflammatory milieu in the lower genital tract and help further our understanding of how BV affects susceptibility to microbial infections.