The anti-inflammatory effect of combined complement and cd14 inhibition is preserved during escalating bacterial load (original) (raw)

2015, Clinical and experimental immunology

Combined inhibition of complement and CD14 is known to attenuate bacterial-induced inflammation, but the dependency of the bacterial load on this effect is unknown. Thus, we investigated whether the effect of such combined inhibition on Escherichia coli- and Staphylococcus aureus-induced inflammation was preserved during increasing bacterial concentrations. Human whole blood was preincubated with anti-CD14, eculizumab (C5-inhibitor) or compstatin (C3-inhibitor), or combinations thereof. Then heat-inactivated bacteria were added at final concentrations of 5x10(4) -1x10(8) /mL (E. coli) or 5x10(7) -4x10(8) /mL (S. aureus). Inflammatory markers were measured using ELISA, multiplex technology and flow cytometry. Combined inhibition of complement and CD14 significantly (P<0.05) reduced E. coli-induced IL-6 by 40-92% at all bacterial concentrations. IL-1β, IL-8 and MIP-1α were significantly (P<0.05) inhibited by 53-100%, and the effect was lost only at the highest bacterial concentr...