Interleukin‐2 induces activation of coagulation and fibrinolysis: resemblance to the changes seen during experimental endotoxaemia
- 1 October 1992
- journal article
- Published by Wiley in British Journal of Haematology
- Vol. 82 (2), 295-301
- https://doi.org/10.1111/j.1365-2141.1992.tb06421.x
Abstract
Summary. 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 × 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 66.48±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.Keywords
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