  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.
