Antithrombin acts as a negative acute phase protein as established with studies on HepG2 cells and in baboons
Niessen, R.W.; Lamping, R.J.; Jansen, P.M.; Prins, M.H.; Peters, M.; Taylor, F.B.; de Vijlder, J.J.; ten Cate, J.W.; Hack, C.E.; Sturk, A.
Thrombosis and Haemostasis 78(3): 1088-1092
1997
ISSN/ISBN: 0340-6245 PMID: 9308758 Document Number: 479055
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, IL-1-beta, 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-1-beta (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 mu-g IL-6 cntdot kg body-weight-1 cntdot day-1 showed increased plasma CRP levels (59-fold, p lt 0.05) and decreased prealbumin (0.9-fold, p lt 0.05) and antithrombin (0.8-fold, p lt 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.