Figure 8.

Dynamical modeling analyses of cytokine network regulation. (A) Simulation of our in vitro cytokine model cannot account for in vivo dynamics under conditions of either continuous (dashed) or transient (solid) LPS stimulation. (B) Literature-based data-driven cytokine interaction network based on in vivo data. (C) In silico model simulations of in vivo cytokine network dynamics (see Methods and Discussion for further explanation of this model). (D) Simulations of wildtype (WT; black) and IL-10 KO; magenta) model TNFα response to a range of LPS stimulus magnitudes (arbitrary units). (E) Analytic framework for computing adaptive recovery of the TNFα response to LPS. (F) LPS concentration response profiles for adaptation of WT and IL-10 KO phenotypes in silico show that the IL-10 KO enhances adaptation to LPS (left-shifted curve).