Caffeic acid phenethyl ester modifies the Th1/Th2 balance in ileal mucosa after γ-irradiation in the rat by modulating the cytokine pattern

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 gamma-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-12R beta 2), Th cytokine responses (IFN-gamma, 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-gamma, 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 intestinal gamma-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. (C) 2006 The WJG Press. All rights reserved.