Totzke G, Smolny M, Seibel M, Czechowski M, Schobersberger W, Hoffmann G
Department of Physiology I, University of Bonn, Nussallee 11, 53115 Bonn, Germany.
Cell Immunol. 2001 Feb 25;208(1):1-8. doi: 10.1006/cimm.2001.1762.
Evidence suggests that antithrombin III (ATIII) exerts anti-inflammatory properties in addition to its anti-coagulative mechanisms. In animal models of sepsis, ATIII affected cytokine plasma concentrations with a decrease of pro-inflammatory cytokines. In addition to cytokines, excessive production of nitric oxide (NO) derived from inducible nitric oxide synthase (iNOS) might represent another important mediator of the cytotoxic events during sepsis. Regarding ATIII as a potential anti-inflammatory modulator, one may speculate that ATIII inhibits the synthesis of iNOS-derived NO. However, our data demonstrate that ATIII further stimulates iNOS gene expression when applied together with either interleukin-1 beta or the combination of lipopolysaccharide plus interferon-gamma. The most prominent synergistic effects on NO synthesis were found when ATIII was given at higher concentrations (1, 5, and 10 U/ml). Although the mechanisms of ATIII signal transduction remain to be established, intensification of interleukin-1 beta or interferon-gamma/lipopolysaccharide-induced NO synthesis by ATIII does not attribute to the anti-inflammatory properties of ATIII.
有证据表明，抗凝血酶III（ATIII）除了具有抗凝血机制外，还具有抗炎特性。在脓毒症动物模型中，ATIII会影响细胞因子的血浆浓度，使促炎细胞因子减少。除细胞因子外，诱导型一氧化氮合酶（iNOS）产生的过量一氧化氮（NO）可能是脓毒症期间细胞毒性事件的另一个重要介质。将ATIII视为一种潜在的抗炎调节剂，有人可能会推测ATIII会抑制iNOS衍生的NO的合成。然而，我们的数据表明，当ATIII与白细胞介素-1β或脂多糖加干扰素-γ联合使用时，会进一步刺激iNOS基因表达。当给予较高浓度（1、5和10 U/ml）的ATIII时，发现对NO合成有最显著的协同作用。尽管ATIII信号转导的机制仍有待确定，但ATIII增强白细胞介素-1β或干扰素-γ/脂多糖诱导的NO合成并不归因于ATIII的抗炎特性。
