Sepsis research in the next millennium: concentrate on the software rather than the hardware.

Today the basic principles of septic conditions are understood. Nevertheless, sepsis research has reached a critical point. To integrate our knowledge towards a consistent theory of the disease process and to derive effective therapies, new perspectives for future research that fit the complexity of the problem have to be found. We conducted a review of the literature concerning systemic inflammatory response syndrome (SIRS) and sepsis with particular reference to liver pathophysiology. And compared our findings with characteristic features of complex systems. The complexity of sepsis is broadly recognized. A review of the different aspects of liver inflammation during SIRS and sepsis, i.e. endotoxin challenge, cytokine induced dysfunction, the mechanisms of leukocyte transmigration, and hormonal and neuroendocrine regulatory mechanisms is given. Key aspects of complex systems, including parallelism, locality, emergence, and cross-scale interactions are introduced. We conclude that sepsis research needs new perspectives that allow us to handle the complex interactions occurring during the disease process. We propose to focus research on the interactions between the constituents of the system rather than only describing isolated aspects of the disease process. We also conclude that the ideas and techniques of non-linear systems theory are suitable tools for the analysis of complex and dynamic diseases like SIRS and sepsis.