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Published on: June 15, 2019
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An In-Silico Study on the Design of Biological Controllers for Sepsis Regulation
Derrick Dankwa1, Syeda Simra Shoaib2, Leopold N Green1
1Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 47905, United States.
ACS Omega
|March 30, 2026
Summary
This study models macrophage behavior in sepsis to design feedback controllers that enhance pathogen clearance and reduce inflammation. Mathematical modeling and simulations show these controllers can successfully resolve infections, even with biological variability.
Area of Science:
- Immunology
- Systems Biology
- Computational Biology
Background:
- Macrophages dynamically shift between M1 (proinflammatory) and M2 (anti-inflammatory) states, crucial for balancing immune defense and tissue repair.
- Sepsis disrupts this macrophage balance, impairing pathogen clearance and exacerbating tissue damage.
Purpose of the Study:
- To develop a mathematical model integrating ordinary differential equations (ODEs) and feedback control to design interventions for sepsis.
- To identify macrophage-mediated regulation as a key factor in sepsis outcomes.
- To design IL-6-responsive feedback controllers to enhance M1 macrophage pathogen clearance.
Main Methods:
- Developed a mathematical model using ODEs and a feedback control framework.
- Analyzed system dynamics based on immune cell behavior and signaling.
- Designed and simulated IL-6-responsive feedback controllers.
Main Results:
- Model highlights macrophage regulation as critical for infection outcomes.
- Simulations demonstrated controller efficacy in regulating septic conditions, achieving up to 95% infection resolution.
- Controllers showed robustness against biological variability and secondary infections.
Conclusions:
- Model-based feedback controllers can effectively modulate sepsis-induced inflammation.
- Findings guide the design of biological controllers for pro-resolving immune states in sepsis.
- Targeted interventions can restore macrophage balance for improved sepsis management.
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