Vodovotz Yoram
Department of Surgery, University of Pittsburgh, and Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Immunol Res. 2006;36(1-3):237-45. doi: 10.1385/IR:36:1:237.
Various stresses elicit an acute, complex inflammatory response, leading to healing but sometimes also to organ dysfunction and death. We constructed both equation-based models (EBM) and agent-based models (ABM) of various degrees of granularity--which encompass the dynamics of relevant cells, cytokines, and the resulting global tissue dysfunction--in order to begin to unravel these inflammatory interactions. The EBMs describe and predict various features of septic shock and trauma/hemorrhage (including the response to anthrax, preconditioning phenomena, and irreversible hemorrhage) and were used to simulate anti-inflammatory strategies in clinical trials. The ABMs that describe the interrelationship between inflammation and wound healing yielded insights into intestinal healing in necrotizing enterocolitis, vocal fold healing during phonotrauma, and skin healing in the setting of diabetic foot ulcers. Modeling may help in understanding the complex interactions among the components of inflammation and response to stress, and therefore aid in the development of novel therapies and diagnostics.
各种应激会引发急性、复杂的炎症反应，炎症反应会促进愈合，但有时也会导致器官功能障碍甚至死亡。我们构建了不同粒度的基于方程的模型（EBM）和基于主体的模型（ABM），这些模型涵盖了相关细胞、细胞因子的动态变化以及由此导致的整体组织功能障碍，以便开始揭示这些炎症相互作用。EBM描述并预测了脓毒症休克和创伤/出血的各种特征（包括对炭疽的反应、预处理现象和不可逆出血），并用于模拟临床试验中的抗炎策略。描述炎症与伤口愈合之间相互关系的ABM，为坏死性小肠结肠炎中的肠道愈合、发声创伤期间的声带愈合以及糖尿病足溃疡情况下的皮肤愈合提供了见解。建模可能有助于理解炎症各组成部分之间的复杂相互作用以及对应激的反应，从而有助于开发新的治疗方法和诊断方法。
