Thus, this 43% reduction in plasma IL-1β detected during LPS-induced endotoxemia—attributable to a loss of C5aR1 signaling—strongly suggested that C5a engages C5aR1 in vivo to amplify TLR4-mediated IL-1β production in the endotoxemia model. Here, TLR4 is linked to serum lipopolysaccharide activity.