Abstract
Due to the inherent complexities involved in understanding a redundant, non-linear process like inflammation, systems biology modeling approaches have been proposed. While these models have produced encouraging results, they do not take into account the circadian nature of many of their components. Circadian rhythms are daily variations in a wide number of biological processes, including many of the hormones and cytokines responsible for the regulation of inflammation. Thus, to work towards the development of a more complete and useful model of inflammation, we extend previous modeling efforts by incorporating important interactions that give rise to circadian variability in inflammation. This is predicated on the assumption that hormones regulated by the central circadian pacemaker ultimately govern diurnal variations in the inflammatory response. The model is then used to simulate a normal resting state, a healthy self-limited inflammatory response, and an unresolved inflammatory response, by analyzing how these responses change throughout the day, clinically-relevant insight is gained.