Inflammation index regulation by modifying the model parameters identified in the sensitivity and correlation analyses.

Shown are the normalized total neutrophil (a) and total macrophage (b) concentrations during chronic (solid red) inflammation. We simulated chronic inflammation by increasing the macrophage influx rate parameter by 5 fold, a strategy we employed in our previous model [11]. These curves appeared in our previous model results (see Figure 5 in [11]) and are reproduced here for comparison purposes. Neutrophil restoration modifications included increasing the CXCL8 degradation rate by 5 fold (solid black), increasing the TGF-β degradation rate by 15 fold (dashed black), and increasing TNF-α inhibition by TGF-β by 5 fold (dotted black). Macrophage restoration modifications comprised increasing the TNF-α degradation rate by 20 fold (black solid), increasing the macrophage efflux rate by 2 fold (dashed black), and increasing IL-10 production rate by 5 fold (dotted black). These parameter-specific fold changes were chosen so as to reduce the respective parameter-specific target inflammation indices by at least ~10% during a chronic inflammatory scenario (the target indices are defined in the description of the six parameter modification strategies in the Results Section). All the model-predicted values were normalized to the respective maximum values from the chronic inflammation simulations. The tables in the figure show the quantitative index values calculated from the respective simulated kinetic trajectories.