A physiological model of the inflammatory-thermal-pain-cardiovascular interactions during a pathogen challenge

TL;DR

This paper presents a mathematical model exploring the interactions between inflammation, thermal regulation, pain, and cardiovascular responses during pathogen challenges, aiming to improve understanding and treatment of systemic inflammatory issues.

Contribution

It introduces a novel integrated physiological model of inflammatory and autonomic interactions calibrated with human and animal data, addressing the gap in understanding the inflammatory impact on autonomic control.

Findings

Multimodal treatment improves recovery outcomes.

Model accurately simulates inflammatory responses.

Targeting both pathogen and symptoms is most effective.

Abstract

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.