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Interleukin‐2 induces activation of coagulation and fibrinolysis: resemblance to the changes seen during experimental endotoxaemia
Author(s) -
Baars Johanna W.,
Boer Jan Paul,
Wagstaff John,
Roem Dorina,
EerenbergBelmer Anke J. M.,
Nauta Jos,
Pinedo Herbert M.,
Hack C. Erik
Publication year - 1992
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1992.tb06421.x
Subject(s) - fibrinolysis , plasminogen activator , medicine , tissue plasminogen activator , antithrombin , endocrinology , coagulation , plasmin , t plasminogen activator , protein c , interleukin , cytokine , chemistry , heparin , enzyme , biochemistry
S ummary . 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 × 10 6 IU/m 2 /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.