  In this study, we provide a dynamical systems perspective to the modelling of
pathological states induced by tumors or infection. A unified disease model is
established using the innate immune system as the reference point. We propose a
two-layer network model for carcinogenesis and sepsis based upon the
interaction of parenchymal cells and immune cells via cytokines, and the
co-evolutionary dynamics of parenchymal, immune cells, and cytokines. Our aim
is to show that the complex cellular cooperation between parenchyma and stroma
(immune layer) in the physiological and pathological case can be qualitatively
and functionally described by a simple paradigmatic model of phase oscillators.
By this, we explain carcinogenesis, tumor progression, and sepsis by
destabilization of the healthy homeostatic state (frequency synchronized), and
emergence of a pathological state (desynchronized or multifrequency cluster).
The coupled dynamics of parenchymal cells (metabolism) and nonspecific immune
cells (reaction of innate immune system) are represented by nodes of a duplex
layer. The cytokine interaction is modeled by adaptive coupling weights between
the nodes representing the immune cells (with fast adaptation time scale) and
the parenchymal cells (slow adaptation time scale) and between the pairs of
parenchymal and immune cells in the duplex network (fixed bidirectional
coupling). Thereby, carcinogenesis, organ dysfunction in sepsis, and recurrence
risk can be described in a correct functional context.
