A pathogenic, surgical, or wound-related threat to the body enacts a complex immune response that, when successful, eradicates the threat and returns the body to homeostasis. Two subsystems that play a key role in regulating inflammation from the immune response include the hypothalamic-pituitary-adrenal (HPA) axis and the cardiovascular system. The dynamics of inflammation, the HPA axis, and the cardiovascular system have been extensively studied individually and on different time scales, but our model is the first to study the interactions of all three subsystems over a 24-hour period. We develop an inflammatory-stress-cardiovascular model which incorporates interactions between inflammatory components (monocytes and major pro- and anti-inflammatory cytokines), hormones secreted by the HPA axis, and major cardiovascular markers (blood pressure, heart rate, and vascular resistance) during an endotoxin (LPS) challenge. As regulators of these model elements, we also incorporate pain, thermal, and nitric oxide effects into the model. This delay differential equation model is fit to mean data from two separate studies both administering a 2 ng/kg bolus dose of endotoxin. Using this model, we study the effects of changes in timing, total dosage amount, and administration methods of the endotoxin.
A mathematical model of inflammatory-stress-cardiovascular dynamics in response to an endotoxin challenge
Kristen A Windoloski, North Carolina State University
2022 AWM Research Symposium