Understanding homeostatic dynamics of the HPA axis using a glucocorticoid pulsatile model

In silico models are often constructed to aid in the understanding of disease and the production of relevant intervention strategies. Several existing models study the acute inflammatory response, which is of importance in multiple organ dysfunction syndrome and sepsis, both of which have high mortality rates. However, no current model of inflammation considers the unique secretory dynamics of cortisol whose secretion has been hypothesized to drive rhythms in key components of the inflammatory response. Cortisol is secreted in a pulsatile and circadian manner, and these characteristics vary with stress. These variations cause both changes in the dynamics of the inflammatory response because they drive the variability in cytokine and hormone production as well as intrinsically relay important information about the system. Changes in feedback within the hypothalamic-pituatary-adrenal axis alter the pulsatile pattern of cortisol secretion, leading to a propagation of events downstream. Here, we build on a previous model of the acute inflammatory response by presenting a method for representing the pulsatile secretion of cortisol in which pulses are the output of a continuous system. Effects on the homeostatic dynamics of the hypothalamic-pituatary-adrenal axis are analyzed as well as its potential in a full inflammatory model.