Mathematical models of the acute inflammatory response

Trauma and infection elicit an acute inflammatory response. In certain circumstances the degree of the acute inflammatory response may result in pathologic manifestations, namely, sepsis and multiple organ failure. Despite an extensive series of clinical trials designed to modulate inflammation in sepsis, only one compound, activated protein C, has emerged from more than 250 failed trials. There is a growing recognition that the complexity of the acute inflammatory response precludes the efficient development of therapies for sepsis and multiple organ failure until systems approaches are brought to bear on this problem.

Work carried out by the authors' groups suggests that mathematical modeling can provide a means by which in vitro and in vivo data can be synthesized into system-level analytic models of the acute inflammatory response. The authors have focused on agent-based modeling and modeling with ordinary differential equations. Some of the advantages and disadvantages of these modeling approaches are presented, and methods for calibration and validation of these models are discussed. Finally, the usefulness of mathematical models to evaluate the prospective therapeutic strategies in clinical trials of sepsis and trauma is examined.

Simulations using various methods can shed insight into the pathophysiology of the acute inflammatory response and may lead to better design of clinical trials in sepsis and trauma.