TNF and cholestasis: Currently, it has been proposed that during ICP the marked increase of E2 and P4 (also their metabolites) provoke cholestasis that negatively modify the immune balance by enhancing the activity of Th1/Th17 cells which release pro-inflammatory cytokines (TNF-α, IFN-γ, IL-17, and IL-6), while decreasing the activity of Th2/Treg cells which produce anti-inflammatory cytokines (IL-10 and IL-4), thus the outcome is multiple organ injury, the comprehensive review by Larson et al. [115] is recommended.