IN-VIVO MODULATION OF COAGULATION AND FIBRINOLYSIS BY RECOMBINANT GLYCOSYLATED HUMAN INTERLEUKIN-6 IN BABOONS

被引:0
|
作者
MESTRIES, JC
KRUITHOF, EKO
GASCON, MP
HERODIN, F
AGAY, D
YTHIER, A
机构
[1] ARES SERONO,DEPT PRECLIN PHARMACOL,CH-1211 GENEVA 20,SWITZERLAND
[2] SERV SANTE ARMEES,CTR RECH,DEPT RADIOBIOL,LA TRONCHE,FRANCE
[3] UNIV LAUSANNE HOSP,CHU VAUDOIS,DEPT MED,DIV HEMATOL,LAUSANNE,SWITZERLAND
关键词
FIBRINOGEN; COAGULATION TESTS; THROMBIN TIME; TISSUE PLASMINOGEN ACTIVATOR; PLASMINOGEN ACTIVATOR INHIBITOR TYPE 1; ACUTE PHASE RESPONSE;
D O I
暂无
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
To assess the effect of interleukin-6 (IL-6) on the coagulation and the fibrinolytic systems, we administered a single subcutaneous injection of recombinant glycosylated human interleukin-6 (r-hIL-6) 100 mu g per kg body weight) to four baboons (Papio ursinus). Four saline injected baboons served as controls. In serial plasma or serum samples collected over a period of seven days we measured several key parameters of the coagulation and the fibrinolytic systems, IL-6 and a set of acute phase proteins. Three hours after the injection, the serum IL-6 levels peaked at 50 ng/ml and then gradually declined with a terminal half-life of around 4 hours. The biological efficacy was demonstrated by the significant increases of several acute phase proteins, circulating platelets and the decrease of prealbumin and fibronectin. Between days 1 and 3, marked effects on the coagulation system were observed with a prolongation of the activated partial thromboplastin time, prothrombin time and thrombin time. Plasma concentrations of fibrinopeptide A and D-dimer increased. The antithrombin III antigen and activity levels decreased, but the thrombin-antithrombin III complex concentrations did not change. The fibrinolytic system rapidly showed striking modifications after 6-8 hours, the concentrations of tissue-type plasminogen activator and of plasminogen activator inhibitor type 1 peaked at respectively four and thirty times the basal concentrations. No changes were seen in the control group. We conclude that besides its well-known acute phase inducing and hematopoietic activities, subcutaneous rhIL-6 also modulates several parameters of the coagulation and the fibrinolytic systems. These are relevant findings for the follow-up of patients under IL-6 therapy and for the understanding of coagulation disorders associated with inflammation or infection.
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页码:275 / 281
页数:7
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