病原体攻击过程中炎症-热痛-心血管相互作用的生理模型
A physiological model of the inflammatory-thermal-pain-cardiovascular interactions during a pathogen challenge
摘要：
免疫细胞和创伤组织中促炎介质的不受控制的过度产生可导致全身性炎症问题，如败血症，这是美国十大死亡原因之一，也是重症监护室的三大死亡原因之一。了解炎症对自主控制系统的影响可以提高患者在手术等炎症事件后恢复的机会。虽然自主反应对炎症系统的影响已经很好地定义，但在理解反向反应方面仍然存在差距。具体而言，炎症反应对自主控制系统的影响仍然未知。在这项研究中，我们调查假设的相互作用的炎症系统与热和心血管调节系统在应对内毒素的挑战，使用数学建模。我们根据两项独立研究的数据校准模型：a）健康年轻男性的炎症反应和b）小鼠和人类之间炎症反应的比较研究。模拟分析用于探索模型如何响应病理输入和治疗，特别是抗生素，解热药，血管加压药和联合治疗。我们的研究结果表明，同时针对病原体和感染症状的多模式治疗提供了最有利的恢复结果。
英文摘要：
Uncontrolled, excessive production of pro-inflammatory mediators from immune cells and traumatized tissues can cause systemic inflammatory issues like sepsis, one of the ten leading causes of death in the United States and one of the three leading causes of death in the intensive care unit. Understanding the effects of inflammation on the autonomic control system can improve a patient's chance of recovery after an inflammatory event such as surgery. Though the effects of the autonomic response on the inflammatory system are well defined, there remains a gap in understanding the reverse response. Specifically, the impact of the inflammatory response on the autonomic control system remains unknown. In this study, we investigate hypothesized interactions of the inflammatory system with the thermal and cardiovascular regulatory systems in response to an endotoxin challenge using mathematical modeling. We calibrate the model to data from two independent studies: a) of the inflammatory response in healthy young men and b) a comparative study of the inflammatory response between mice and humans. Simulation analysis is used to explore how the model responds to pathological input and treatment, specifically antibiotics, antipyretics, vasopressors, and combination therapy. Our findings show that multimodal treatment that simultaneously targets both the pathogen and the infection symptoms gives the most favorable recovery outcome.
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