TNF and Sepsis: Moreover, in vitro studies have shown that GTS-21 suppresses M1 macrophage polarization while promoting M2 macrophage polarization through the upregulation of TNF-α/PI3K and phosphorylation of STAT3 [34,35]; through polarization of macrophage, activation of α7nAChR eventually reduces the systemic inflammatory level in sepsis [9].