Kirchplatz 3, 27305 Bruchhausen-Vilsen, Germany; Institute for Chemistry and Biology of the Marine Environment, Carl von Ossietzky University, Oldenburg, Germany.
Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Germany.
J Theor Biol. 2014 May 7;348:33-46. doi: 10.1016/j.jtbi.2014.01.016. Epub 2014 Jan 28.
In autoimmune diseases, inflammatory cytokine concentrations are important for initiating and maintaining the status of autoimmunity. Autoimmune hepatitis (AIH) is an inflammatory liver disease characterized by a loss of immune tolerance against specific antigens located in hepatocytes. During the progression of the disease, antigen-presenting cells and different classes of T-helper cells secrete specific cytokines important for maintaining the disease. As these cytokines are secreted into the local liver environment, the blood flow in liver sinusoids might influence the local cytokine concentration. Considering the liver tissue as a porous medium, based on Darcy׳s law, the microcirculation within a liver lobule was modelled. Using realistic physiological pressure differences and tissue permeabilities, the blood velocity inside the sinusoids could be calculated and validated with blood velocity data obtained via Orthogonal Polarization Spectral Imaging (OPSI). Furthermore, oxygen consumption is modelled to obtain Rappaport׳s acinus model. Finally, steady state spatial distributions of secreted cytokines within the liver lobule could be estimated for specified realistic production rates of T-helper cells. It could be demonstrated that the characteristics of the liver microcirculation have an important impact on establishing inflammatory cytokine levels within the portal fields and the vascular septa promoting the occurrence of interface hepatitis.
在自身免疫性疾病中，炎症细胞因子的浓度对于启动和维持自身免疫状态非常重要。自身免疫性肝炎（AIH）是一种以肝细胞内特定抗原的免疫耐受丧失为特征的炎症性肝病。在疾病进展过程中，抗原呈递细胞和不同类别的辅助性 T 细胞分泌对维持疾病具有重要意义的特定细胞因子。由于这些细胞因子分泌到局部肝环境中，肝窦的血流可能会影响局部细胞因子浓度。考虑到肝组织为多孔介质，基于达西定律，对肝小叶内的微循环进行建模。利用真实的生理压力差异和组织渗透性，可以计算出窦内的血流速度，并通过正交偏振光谱成像（OPSI）获得的血流速度数据进行验证。此外，还对耗氧量进行建模以获得 Rappaport 的腺泡模型。最后，对于特定的辅助性 T 细胞的现实产生速率，可以估计肝小叶内分泌细胞因子的稳态空间分布。结果表明，肝微循环的特征对门脉区内炎症细胞因子水平的建立以及促进界面肝炎发生的血管隔室具有重要影响。
