Identification of Key Processes that Control Tumor Necrosis Factor Availability in a Tuberculosis Granuloma
Figure 7
Model predictions for the effect of TNF-neutralizing drugs with various properties on the availability of TNF within a granuloma.
(A) Class 1: the drug can only bind to sTNF with a binding ratio of 1∶1. (B) Class 2: the drug can bind to both mTNF and sTNF with a binding ratio of 1∶1. The star shows the location of a drug with TNF binding kinetics similar to etanercept. (C) Class 3: the drug can bind to both mTNF and sTNF with a binding ratio of 3∶1. The star shows the location of a drug with TNF binding kinetics similar to infliximab. (D) Model predictions for the effect of TNF/drug association rate constant on neutralization efficiency of drugs of different classes but identical affinities (Kd_Drug = koff_TNF/Drug/kon_TNF/Drug = 10−9 M). Model parameter values are the same as Figure 6. TNF neutralization-associated parameter values are as listed in Table 4.