Activation of endothelium by immunotherapy with interleukin-2 in patients with malignant disorders

Treatment with intravenous recombinant human interleukin-2, (rh IL-2) is fr equently accompanied by the capillary leak syndrome and disturbances of the coagulation system, Although the exact mechanisms are still not fully unde rstood, the involvement of the endothelium is proven. This investigation ai med to elucidate more precisely the role of the endothelium in the generati on of IL-2-based side-effects. In nine tumour patients receiving intravenou s rh IL-2, parameters characterizing endothelial cell activation as well as activation of the coagulation system were evaluated. A significant increas e of the circulating endothelial leucocyte adhesion molecule-1 (cELAM-1) an d the vasoconstrictor peptide endothelin-1 (ET-1) was observed (P < 0.05), indicating activation of endothelial cells, The simultaneous increase of ti ssue-plasminogen activator and plasminogen activator inhibitor type-1 durin g therapy (P < 0.05) corroborated this observation. A decrease in platelet count parallelled by an increase of fibrin degradation products, the prolon gation of partial thromboplastin time, and the decrease of fibrinogen (P < 0.05) suggested. the development of disseminated intravascular coagulation (DIC), induced by activated endothelium and intensified by transient hepati c failure. We concluded that activation of the endothelium mediated by IL-2 was accompanied by a loss of endothelial integrity and capillary leak. The activated endothelium can trigger DIC via activation of the coagulation ca scade, The increased ET-1 might act as an endogenous counter-regulator of t he disadvantageous haemodynamic side-effects induced by IL-2.