INTERLEUKIN-2 INDUCES ACTIVATION OF COAGULATION AND FIBRINOLYSIS - RESEMBLANCE TO THE CHANGES SEEN DURING EXPERIMENTAL ENDOTOXEMIA

The administration of Interleukin-2 (IL-2) causes the release or generation of other cytokines such as tumour necrosis factor (TNF) which. by disturbing the anticoagulant properties of the endothelium, may induce a procoagulant state in patients receiving this drug. We therefore evaluated the effects of IL-2 on coagulation and fibrinolysis in 14 patients receiving 12 or 18 x 10(6) IU/m2/d of IL-2 given as a 15 min infusion for 5 d. Blood samples were drawn at short intervals after the first IL-2 infusion. The parameters were analysed by way of analysis for repeated measures (F tests rather than t tests). During the first day, thrombin-antithrombin (TAT) complexes started to increase 2 h after the IL-2 infusion, reaching peak levels at 4 h (n = 14; 11.2+/-6.4 ug/l nu 49.8+/-49.2 mug/l, P < 0.01). Plasmin alpha2 antiplasmin (PAP) complexes showed a similar pattern rising from a mean baseline value of 17.5+/-7.6 nmol/l to 66.8+/-47.7 nmol at 4 h (P < 0.01). In four patients the peak of PAP preceeded that of TAT. Tissue plasminogen activator (tPA) rose from a mean baseline value of 4.9+/-3.7 mug/l to 26.3+/-13.5 mug/l at 4 h (P < 0.01). Plasminogen-activator-inhibitor-1 (PAI-1) levels increased from 59+/-35 mug/l to 113+/-39 mug/l at 6 h (P < 0.01). tPA PAI-l complexes increased from 0.15+/-0.07 to 0.69+/-0.21 nmol/l at 6 h (P < 0.01). Our study indicates that IL-2 activates the coagulation and fibrinolytic systems in vivo. The changes resemble the perturbations observed after endotoxin/TNF administration. These abnormalities may play a role in the side-effects induced by IL-2 therapy.