siRNA silencing IL-12p40 reduces local and systemic levels of IL-12p40 protein. LPS delivery to the peritoneal cavity with simultaneous (white bars), or therapeutic administration (black bars) of IL-12p40 specific siRNA reduced the appearance of IL-12p40 protein in serum (A) and peritoneal lavage (B) as measured by IL-12p40 specific ELISA. Serum and lavage were sampled at 6 h post LPS challenge. IL-12p40 observed in serum or lavage from LPS challenged mice or mice co-challenged with LPS and either GFPsiRNA or Mut.siRNA was significantly greater than control (p < 0.05, in both cases). IL-12p40 siRNA when delivered simultaneously or therapeutically significantly reduced IL-12p40 protein production compared to LPS challenge alone (p < 0.05, in each case). Data are representative of three independent experiments where n = 4 on each occasion; IL-12p40 protein concentration is expressed as the mean (+/-SEM) from triplicate samples.