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Thromb Haemost 1997; 78(03): 1088-1092
DOI: 10.1055/s-0038-1657691
Rapid Communication
Schattauer GmbH Stuttgart

Antithrombin Acts as a Negative Acute Phase Protein as Established with Studies on HepG2 Cells and in Baboons

R W L M Niessen
1   The Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Amsterdam, The Netherlands
2   The EKZ/Children's AMC, Amsterdam, The Netherlands
,
R J Lamping
1   The Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Amsterdam, The Netherlands
,
P M Jansen
4   The Department of Autoimmune Disease, Central Laboratory of the Netherlands Blood Transfusion Service, Amsterdam, The Netherlands
,
M H Prins
3   The Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, Amsterdam, The Netherlands
,
M Peters
2   The EKZ/Children's AMC, Amsterdam, The Netherlands
,
F B Taylor Jr.
6   The Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, USA
,
J J M de Vijlder
2   The EKZ/Children's AMC, Amsterdam, The Netherlands
,
J W ten Cate
1   The Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Amsterdam, The Netherlands
,
C E Hack
4   The Department of Autoimmune Disease, Central Laboratory of the Netherlands Blood Transfusion Service, Amsterdam, The Netherlands
,
A Sturk
5   The Department of Clinical Chemistry, Academic Hospital Leiden, Leiden, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 24 1997

Accepted 12 May 1997

Publication Date:
12 July 2018 (online)

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Summary

Patients with sepsis or after major surgery have decreased plasma levels of the anticoagulant protein antithrombin. In such patients elevated levels of interleukin-6 (IL-6) are present and this interleukin is known to induce positive and negative acute phase responses. To investigate the possibility that antithrombin acts as a negative acute phase response-protein we performed studies on the human hepatoma cell line HepG2 in vitro and baboons in vivo. HepG2 cells were treated with recombinant human IL-6, ILß3, or combinations of the latter two, and tested for production of antithrombin, fibrinogen and prealbumin (transthyretin). This treatment resulted in a dose dependent increase in fibrinogen concentration (with a maximum effect of 2.8-2.9-fold) and a dose dependent decrease in prealbumin (with a maximum effect of 0.6-0.7-fold) and antithrombin concentrations (with a maximum effect of 0.6-0.8-fold). Simultaneous treatment of the HepG2 cells with IL-6 (1,000 pg/ml or 2,500 pg/ml) and IL-1β (25 pg/ml), provided more extensively decreased prealbumin (0.8 and 0.6-fold, respectively) and antithrombin concentration (0.7 and 0.6-fold, respectively) compared to the single interleukin treatment at these concentrations. Baboons treated with 2 µg IL-6 · kg body-weight-1 · day1 showed increased plasma CRP levels (59-fold, p <0.05) and decreased prealbumin (0.9-fold, p <0.05) and antithrombin (0.8-fold, p <0.05) plasma levels, without evidence for coagulation activation. Our results indicate that antithrombin acts as a negative acute phase protein, which may contribute to the decreased antithrombin plasma levels observed after major surgery or in sepsis.

 

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