Interleukin-2 induces activation of coagulation and fibrinolysis: Resemblance to the changes seen during experimental endotoxaemia

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 10⁶ 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 μg/l v 49.8 ± 49.2 μg/l, P <0.01). Plasmin α2 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 μg/l to 26.3 ± 13.5 μg/l at 4 h (P <0.01). Plasminogen-activator-inhibitor-1 (PAI-1) levels increased from 59 ± 35 μg/l to 113 ± 39 μg/l at 6 h (P <0.01). tPA PAI-1 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.