Multiscale Equation-Based Models: Insights for Inflammation and Physiological Variability

The inflammatory response initiates the healing and recovery from injury. When successful, this leads to the restoration of homeostasis; however, if homeostasis cannot be restored, elevated levels of inflammatory activity may exert a deleterious effect. Given the complexity inherent in the redundant and interacting components of the inflammatory response, the development of novel therapies aimed at modulating the inflammatory response has been slow. In this chapter, we discuss our work on modeling human endotoxemia while focusing on how physiologic variability plays a role in the inflammatory response and how rhythmic biological signals may be applied in a translational context. Physiologic variability, ranging in scale from oscillations in autonomic activity less than 1 Hz which are reflected in short-term heart rate variability (HRV) to circadian rhythms in cytokine and hormone activities, is generally disrupted in inflammation. Based on this, the opportunity exists to study biological rhythms to gain insight into underlying physiological mechanisms and identify clinically relevant information.