GPR81 is required for dampening pro-inflammatory responses and for lactate mediated immunomodulation in vivo. Gpr81 expression in isolated liver cell populations (A). Inflammatory gene induction in response to LPS, CpG, and lactate in isolated Kupffer cells (A). Western blot and densitometry from liver lysates of mice treated with siRNA scramble or siRNA for Gpr81 probed with anti-GPR81 antibody (B). Mice were treated with siRNA for Gpr81 or siRNA scramble, LPS and galactosamine, and pretreated with lactate or PBS by intraperitoneal injection. Induction of inflammatory genes in the liver (C), liver histology scoring and representative histology (D), serum ALT values (E), and survival data (F). Asterisks denote significant difference (P<0.05) between bracketed groups. NS, not significant.