InterJournal Complex Systems, 344
Status: Accepted
Manuscript Number: [344]
Submission Date: 413
Complexity, Emergence and Pathophysiology: Using Agent Based Computer Simulation to characterize the Non-Adaptive Inflammation Response
Author(s): Gary An

Subject(s): CX.31, CX.32, CX.33, CX.63

Category: Brief Article

Abstract:

The non-adaptive inflammatory response is a complex system that maintains the human body against injury. However, severe perturbations to this system may lead to pathologic conditions in which the system behaves in paradoxical fashion. The clinical manifestation of this is Systemic Inflammatory Response Syndrome (SIRS). The management of SIRS represents the greatest challenge in critical care medicine. Although many of the mediators of this process have been characterized, attempts to manipulate the course of the disease using this knowledge have been unsuccessful, even detrimental. There is a gap between the physiologic manifestations of SIRS/MOF and the underlying cellular/molecular pathophysiology. We propose that clinically apparent organ-level physiology represents emergent properties of the underlying cellular/molecular mechanisms. A failure to account for the nonlinear, complex nature of the inflammatory response is a failure to recognize the emergent basis of the physiologic organ response, and is the root of the difficulty in formulating effective treatment regimes. We propose that Agent-Based Computer Simulation (ABCS) may be a means to characterize the dynamics of the inflammatory response. Using the known cellular and molecular mediators of the process as agents it may be possible to construct models that would help define the state spaces of the inflammatory response, including identification of phase transitions between the "normal", dynamically stable state and its unstable, pathologic state (SIRS). ABCS is envisioned as an engineering tool in designing treatment regimes and as an aid in the understanding of how the various components of the system interact to produce organ-level physiology.

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