The present study investigates the relative ability of α-Toc, -Toc and -Toc to modulate cell signaling events that are associated with inflammatory responses in fetal-derived (FHs 74 Int) intestinal cells. The secretion of pro-inflammatory IL8 cytokine secretion in FHs 74 Int cells was stimulated in the order α–Toc< – Toc < – Toc. A similar pro-inflammatory response was observed when inflammation was induced in FHs 74 Int cells. The effect of Toc to modulate IL8 expression corresponded to an isoform-specific modulation of NfB and Nrf-2 cell signaling pathways involved in the expression of pro-inflammatory cytokines and antioxidant enzymes, respectively. Delta-Toc and to a lesser extent -Toc activated both NfB and Nrf-2 signaling, as indicated by the greater nuclear translocation of transcription factors. Activation of NfB signaling by - and -Toc was accompanied by the up-regulation of NfB target genes, such as IL8 and PTGS2, occurring both with and without a prior IFN/PMA challenge. Nevertheless, - and -Tocs, particularly -Toc, concurrently down-regulated glutatamate cysteine ligase (GCLC), a Nrf-2 target gene that encodes for glutathione biosynthesis. Substantiation of this observation was made by confirming that both -Toc and -Toc were effective at decreasing GCLC protein expression and cellular glutathione content. Down-regulation of the glutathione content in fetal intestinal cells corresponded to the induction of apoptosis-mediated cytotoxicity. In conclusion, - and -Tocs are biologically active forms of vit E and show superior bioactivity to α-Toc in modulating cell signaling events that contribute to a pro-inflammatory response in fetal-derived intestinal cells.