Agent-based computer simulation and SIRS: Building a bridge between basic science and clinical trials

The management of Systemic Inflammatory Response Syndrome (SIRS)/Multiple Organ Failure (MOF) remains the greatest challenge in the field of critical care. There has been uniform difficulty in translating the results of basic science research into effective therapeutic regimes. We propose that this is due in part to a failure to account for the complex, nonlinear nature of the inflammatory process of which SIRS/MOF represents a disordered state. Attempts to manipulate this process without an understanding of the dynamics of the system may potentially produce unintended consequences. Agent-Based Computer Simulation (ABCS) provides a means to synthesize the information acquired from the linear analysis of basic science into a model that preserves the complexity of the inflammatory system. We have constructed an abstracted version of the inflammatory process using an ABCS that is based at the cellular level. Despite its abstraction, the simulation produces non-linear behavior and reproduces the dynamic structure of the inflammatory response. Furthermore, adjustment of the simulation to model one of the unsuccessful initial anti-inflammatory trials of the 1990's demonstrates the adverse outcome that was observed in those clinical trials. It must be emphasized that the current model is extremely abstract and simplified. However, it is hoped that future ABCSs of sufficient sophistication eventually may provide an important bridging tool to translate basic science discoveries into clinical applications. Creating these simulations will require a large collaborative effort, and it is hoped that this paper will stimulate interest in this form of analysis.