Predominant inhibition of interleukin-6 synthesis in patient-specific endothelial cells by mTOR inhibitors below a concentration range where cell proliferation is affected and mitotic arrest takes place.

UNLABELLED: Organ rejection and inflammation are accompanied by endothelial cell activation. An in vitro model with patient-specific endothelial cells was used to study the impact of mTOR inhibitors on cell growth and release of proinflammatory cytokines.
MATERIAL AND METHODS: Confluent monolayers of human saphenous vein endothelial cells were pretreated with everolimus or sirolimus followed by induction with tumour necrosis factor-alpha (TNF-alpha).
RESULTS: Incubation with sirolimus or everolimus resulted in a dose-dependent deceleration of cell growth. Compared to control, cell count at high concentrations ceased to increase and remained at 60%. This mitotic arrest was accompanied by a dose-dependent inhibition of the TNF-alpha-induced in situ synthesis and release of interleukin-6 per cell by 60%.
CONCLUSIONS: Under conditions mimicking cytokine-induced cell activation a predominant inhibitory effect of everolimus compared to sirolimus on endothelial cell proliferation was observed paralleled by an inhibition of proinflammatory cytokines. This might attenuate the acute proinflammatory status after transplantation.