AIM: To pharmacologically modulate Th polarization in the ileum exposed to ionizing radiation by using the immuno-modulatory/apoptotic properties of Caffeic Acid Phenethyl Ester (CAPE). METHODS: Rats received CAPE (30 mg/kg) treatment ip 15 min prior to intestinal 10 Gyγ-irradiation and once a day for a 6 d period after irradiation. Expression of genes implicated in Th differentiation in ileal mucosa (IL-23/IL-12Rβ2), Th cytokine responses (IFN-γ, IL-2, IL-4, IL-13), Th migratory behaviour (CXCR3, CCR5, CCR4), Th signalling suppressors (SOCS1, SOCS3), transcription factor (T-Bet, GATA-3) and apoptosis (FasL/Fas, TNF/TNFR, XIAP, Bax, caspase-3) was analyzed by RT-PCR 6 h and 7 d post-irradiation. CD4+ and TUNEL positive cells were visualized by immunostaining. RESULTS: The expression of Th1-related cytokine/ chemokine receptors (IFN-γ, IL-2, CXCR3, CCR5) was repressed at 7 d post-irradiation while Th2 cell cytokine/ chemokines (IL-4, IL-13, CCR4) were not repressed or even upregulated. The irradiation-induced Th2 profile was confirmed by the upregulation of both Th2-specific transcription factor GATA-3 and SOCS3. Although an apoptosis event occurred 6 h after 10 Gy of intestinalγ-irradiation, apoptotic mediator analysis showed a tendency to apoptotic resistance 7 d post-irradiation. CAPE amplified apoptotic events at 6h and normalized Bax/ FasL expressions at 7 d. CONCLUSION: CAPE prevented the ileal Th2 immune response by modulating the irradiation-influenced cytokine environment and apoptosis. AIM: To pharmacologically modulate Th polarization in the ileum exposed to ionizing radiation by using the immuno-modulatory / apoptotic properties of Caffeic Acid Phenethyl Ester (CAPE). METHODS: Rats received CAPE (30 mg / kg) treatment ip 15 min prior to intestinal 10 Gy γ-irradiation and once a day for a 6 d period after irradiation. Expression of genes implicated in Th differentiation in ileal mucosa (IL-23 / IL-12Rβ2), Th cytokine responses (IFN-γ, IL- (T-Bet, GATA-3) and apoptosis (FasL / Fas, TNF / TNFR, XIAP4), Th migratory behavior (CXCR3, CCR5, CCR4), Th signaling suppressors (SOCS1, SOCS3) , Bax, caspase-3) was analyzed by RT-PCR 6 h and 7 d post-irradiation. CD4: TUNEL positive cells were visualized by immunostaining. RESULTS: The expression of Th1-related cytokine / chemokine receptors -2, CXCR3, CCR5) was repressed at 7 d post-irradiation while Th2 cell cytokine / chemokines (IL-4, IL-13, CCR4) were not repressed or even upregulat ed. The irradiation-induced Th2 profile was confirmed by both upregulation of both Th2-specific transcription factor GATA-3 and SOCS3. Although an event event occurred 6 h after 10 Gy of intestinal γ-irradiation, apoptotic mediator analysis showed a tendency to apoptotic resistance 7 days post-irradiation. CAPE amplified apoptotic events at 6h and normalized Bax / FasL expressions at 7 days. CONCLUSION: CAPE prevented the ileal Th2 immune response by modulating the irradiation-influenced cytokine environment and apoptosis.