Biliverdin attenuates LPS-induced pro-inflammatory cytokine expression in whole human blood

Objective: Inflammation is clearly implicated in the pathogenesis of cardiovascular disease, sepsis and respiratory disorders. The present study aimed to reveal the effect of biliverdin (BV) on the expression of pro/anti-inflammatory cytokines in whole human blood.

Methods: Eight healthy males were recruited and 50 mLs of blood was collected into EDTA vacutainers. Whole blood was supplemented with BV (10 or 50 μM) in the presence or absence of 3 μg/mL lipopolysaccride for 4, 8 and 24 hours. Total RNA was purified at 4 h and plasma was collected at 4, 8 and 24 hours. Gene and protein expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-1Ra and IL-10) were analyzed using qRT-PCR and multiplex Luminex analysis.

Results: Biliverdin inhibited LPS-mediated expression of IL-1 β and IL-1Ra in a dose dependent manner, showing a 50% decrease at 4 h (50 μM, P<0.05). However, BV showed only a slight non-significant decrease (69 %) in IL-6 expression under the same conditions while no significant effect was found for TNF-α and IL-10 expression.

Conclusion: Biliverdin reduces LPS-induced expression of IL-1 β and IL-1Ra in whole human blood. This study is the first translational evidence to support BV’s use as anti-inflammatory agent in humans against LPS/sepsis.