Fig 4. Model correctly predicts responses to perturbations in the SMAD4-hepcidin-pathway as well as development of anemia under chronic inflammation.

A-Model quantitatively predicts experimentally measured responses for 2 months old C326S knock-in mice expressing a hepcidin-resistant FPN mutant or or SMAD4-knockout mice. The model simulations are shown as blue bars and the corresponding data from [37] and [53] as red bars, respectively. Fold changes are referred to the wildtype levels. The model error bars are calculated from the predictions of the 30 best fitting parameter sets (see S1 Text). B-Model prediction for body iron pools when ferroportin regulation by hepcidin is out of action in one of the indicated organs. Shown are model simulations whithout experimental validation. C-Model qualitatively reproduces the development of anemia of inflammation upon chronic elevation of body LPS. Simulation of plasma, RBC and liver iron evolution when the inflammatory Il6/STAT pathway is permanently activated by a persistent LPS stimulus (0.17 μg/g body weight). Shown are model simulations without a quantitative comparison to experiments.