CYCLOSPORINE-A INHIBITS HUMAN ENDOTHELIAL-CELLS PROLIFERATION THROUGHINTERLEUKIN-6-DEPENDENT MECHANISMS

Cyclosporine A (CsA) is a widely used immunosuppressant which possesse s significant side effects including nephrotoxicity and systemic arter ial hypertension. In this work we evaluated the effects of CsA on huma n umbilical endothelial cell proliferation (HUVEC). Treatment of endot helial cells with CsA inhibited cell proliferation, and was correlated with an increase of interleukin-6 (IL-6) production and IL-6 mRNA exp ression. Addition of exogenous IL-6 also significantly altered cell pr oliferation. Furthermore, neutralization of endogenous IL-6 with a spe cific monoclonal antibody concomitantly with CsA treatment completly r estored HUVEC proliferation. These results suggest that CsA-induced in hibition of HUVEC proliferation is mediated through an augmentation of IL-6 synthesis.