Fig. 4.

TGFβ and IL-10 provide temporally distinct feedback inhibition to TNFα. (A) Relative waveforms of TNFα, TGFβ, and IL-10 are plotted for comparison (LPS = 1000 starting at t = 0). (B) Normalized TGFβ and IL-10 contributions to the TNFα activation rate equation show that IL-10-mediated inhibition of TNFα precedes that of TGFβ. These quantities were computed as $\begin{array}{l}{K}_{\text{TGF}⊣\text{TNF}}^{n_{\text{TGF}⊣\text{TNF}}}/({\mathit{TGF}}^{n_{\text{TGF}⊣\text{TNF}}}+K_{\text{TGF}⊣\text{TNF}}^{n_{\text{TGF}⊣\text{TNF}}})\\ \end{array}$ and $K_{\text{IL}10⊣\text{TNF}}^{n_{\text{IL}10⊣\text{TNF}}}/(\text{IL}{10}^{n_{\text{IL}10⊣\text{TNF}}}+K_{\text{IL}10⊣\text{TNF}}^{n_{\text{IL}10⊣\text{TNF}}})$. (C) Normalized area under the curve (AUC) was computed as a function of time for the TGFβ and IL-10 inputs to TNFα shown in panel A. The AUC ratio trace represents the fractional contribution of IL-10 relative to TGFβ: AUC ratio = AUC_IL10/(AUC_TGF + AUC_IL10). (D) Cytokine interaction network where sensitive interactions that will be the focus of the remainder of the paper are highlighted.