An In-Silico Study on the Design of Biological Controllers for Sepsis Regulation
Derrick Dankwa, Syeda Simra Shoaib, Leopold N. Green, Xun Tang
TL;DR
This paper uses computer modeling to design biological controllers that can regulate sepsis by influencing macrophage behavior.
Contribution
The novel contribution is the development of IL-6-responsive feedback controllers to enhance pathogen clearance during sepsis.
Findings
Simulation results showed up to 95% success in resolving sepsis using the designed controllers.
The controllers were robust to biological variability and secondary infections.
Macrophage-mediated regulation was identified as a critical driver of infection outcomes.
Abstract
Macrophages are versatile innate immune cells that can dynamically shift between proinflammatory (M1) and anti-inflammatory (M2) states to balance immune defense and tissue repair, in response to local microenvironment cues. In sepsis, disrupted macrophage function impairs this balance, reducing pathogen clearance and increasing tissue damage. To address this, we developed a mathematical model integrating ordinary differential equations (ODEs) and a feedback control framework to design targeted interventions that promote healing. Grounded in the current knowledge of immune cell behavior and signaling, our model highlights macrophage-mediated regulation as a critical driver of infection outcomes. With model-based analysis and a biological understanding about the system dynamics, we designed IL-6-responsive feedback controllers to enhance M1 macrophage-driven pathogen clearance.…
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Taxonomy
TopicsImmune cells in cancer · Immune Response and Inflammation · Immune responses and vaccinations