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

Abstract

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.