In vivo modulation of coagulation and fibrinolysis by recombinant glycosylated human interleukin-6 in baboons.
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 micrograms 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Mestries
J C
JC
Department of Radiobiology, Centre de Recherches du Service de Santé des Armées, La Tronche, France.
Kruithof
E K
EK
Gascon
M P
MP
Herodin
F
F
Agay
D
D
Ythier
A
A
D000210:Acute-Phase Reaction / Q000097:blood; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D005342:Fibrinolysis / Q000187:drug effects*; D006031:Glycosylation; D006801:Humans; D007279:Injections, Subcutaneous; D015850:Interleukin-6 / Q000031:analogs & derivatives / Q000494:pharmacology*; D010215:Papio; D011994:Recombinant Proteins / Q000494:pharmacology
D015850:Interleukin-6; D011994:Recombinant Proteins