Influence of dabigatran on pro-inflammatory cytokines, growth factors and chemokines - Slowing the vicious circle of coagulation and inflammation

Aims: Blood coagulation is one of the most important host-defending mechanisms in vivo by maintaining the blood pressure after injury. However, besides maintaining homeostasis, blood coagulation and the contributing factors are directly linked to pathological conditions, such as thromboembolism and inflammation, leading to cardiovascular diseases, among others. As anti-inflammatory drugs may reduce cardiovascular events, we hypothesized in this study that the direct thrombin inhibitor dabigatran may reduce cytokine, growth factor and chemokine expression in vitro. Main methods: Initially, human whole blood was incubated in tubes for serum, EDTA plasma, and heparinized plasma. Furthermore, human PBMCs were isolated and incubated under different culture conditions, including the treatment with human serum or thrombin, respectively. The effect of the oral anticoagulant dabigatran on pro-inflammatory cytokines, growth factors and chemokines was investigated by ELISA. Key findings: Conditioned serum resulted in a significant alteration of the secretome's protein levels after 24 h. However, solely ANG showed a dose-dependent increment by the addition of serum (79.8 +/- 9.2 ng/mL) in comparison to baseline (0.2 +/- 0.2 ng/mL), as it was in trend for thrombin treatment. Furthermore, the pretreatment of PBMCs with different doses of dabigatran significantly lowered supernatant protein levels measured. Moreover, dabigatran was shown to decrease most notably the growth factor and chemokine levels in the PBMC's secretome that were treated with 200 ng/mL thrombin in a dose-dependent manner. Significance: In conclusion, novel oral anticoagulants, such as dabigatran, could help to reduce not only procoagulatory effects in inflammatory conditions but could also reduce proinflammatory stimuli via reduced expression of cytokines and chemokines.