AIM： To investigate if an immune imbalance may account for the development and progression of chronic radiation enteritis. We analyzed the Th1/Th2 immune response profile early and 6 mo after fractionated colorectal ...AIM： To investigate if an immune imbalance may account for the development and progression of chronic radiation enteritis. We analyzed the Th1/Th2 immune response profile early and 6 mo after fractionated colorectal irradiation. METHODS： A rat model of fractionated colorectal γ-irradiation （4-Gy fractions, 3 fractions per week） was designed to investigate the effects of cumulative dose on inflammatory mediators （cytokines and chemo- kines） and immune response （Th1/Th2 profile and immunosuppressive mediator IL-10） during acute （early） response and 6 mo after the end of fractionated irradiation （chronic response）. Analyses were performed 1 d after the cumulative doses of 16 Gy and 36 Gy and 1 d, 3 d, and 26 wk after the cumulative dose of 52 Gy. RESULTS： Without causing histological damage, fractionated radiation induced elevated expression of IL-1β, TNFα, MCP-1, and iNOS in distal colonic mucosa during the early post-irradiation phase. At that time, a Th2 profile was confirmed by expression of both the Th2- specific transcription factor GATA-3 and the chemokine receptor CCR4 and by suppression of the Thl cytokine IFNγ/IP-10 throughout the irradiation protocol. After 6 mo, despite the 2-fold reduction of iNOS and MCP-1 levels, the Th2 profile persisted, as shown by a 50% reduction in the expression of the Thl transcription factor T-bet, the chemokine receptor CCXCR3, and the IFNγ/ STAT1 pathway. At the same time-point, the immunosuppressive IL-10/STAT3 pathway, known to regulate the Th1/Th2 balance, was expressed, in irradiated rats, at approximately half its level as compared to controls.This suppression was associated with an overexpression of SOCS3, which inhibits the feedback of the Thl polarization and regulates IL-10 production. CONCLUSION： Colorectal irradiation induces Th2 polarization, defective IL-10/STAT3 pathway activation and SOCS3 overexpression. These changes, in turn, maintain a immunological imbalance that persists in the long term.展开更多
In order to investigate the effects of interleukin-18 （IL-18） on airway inflammation and the Th1/Th2 cytokine balance in guinea pig asthmatic model as well as its possible mechanisms, the asthmatic model was establi...In order to investigate the effects of interleukin-18 （IL-18） on airway inflammation and the Th1/Th2 cytokine balance in guinea pig asthmatic model as well as its possible mechanisms, the asthmatic model was established by intraperitoneal injection of ovalbumin （OVA） and aerosol challenges into guinea pigs, and 30 treated animals were randomly divided into three groups of 10 animals in each groups, in which group A served as the asthmatic model, group B as the controls and group C as the group treated with IL-18. The counting and categorization of the inflammatory cells in bronchoalveolar lavage fluid （BALF） were performed by using light microscopy, and the contents of cytokines （ IFN-γ, IL- 2, IL-4 and IL-5） were assayed by means of the ELISA kit. The experimental results showed that the numbers of eosinophils （ESO） in BALF of group A, B and C were （97.70 ± 58.03） × 10^6/L, （11.68 × 9.95） × 10^6/L and （28.62 ± 10.46） × 10^6/L, respectively, in which the number of eosinophils in group A was significantly higher than those of group B and C. Also, the number of neutrophils in BALF of group A was even higher than those in group B and C. In addition, the contents of IFN-7 and IL-2 in group A were lower than those in group B and C, but the contents of IL-4 as well as IL-5 were rather higher than those in group B and C. It is evident from the above observations that IL-18 can effectively inhibit the asthmatic inflammatory cells in BALF with an imbalance of the Thl/Th2 cytokines, thus offer- ing the experimental basis for the clinical application of IL-18 in the prevention and treatment of asthma.展开更多
文摘AIM： To investigate if an immune imbalance may account for the development and progression of chronic radiation enteritis. We analyzed the Th1/Th2 immune response profile early and 6 mo after fractionated colorectal irradiation. METHODS： A rat model of fractionated colorectal γ-irradiation （4-Gy fractions, 3 fractions per week） was designed to investigate the effects of cumulative dose on inflammatory mediators （cytokines and chemo- kines） and immune response （Th1/Th2 profile and immunosuppressive mediator IL-10） during acute （early） response and 6 mo after the end of fractionated irradiation （chronic response）. Analyses were performed 1 d after the cumulative doses of 16 Gy and 36 Gy and 1 d, 3 d, and 26 wk after the cumulative dose of 52 Gy. RESULTS： Without causing histological damage, fractionated radiation induced elevated expression of IL-1β, TNFα, MCP-1, and iNOS in distal colonic mucosa during the early post-irradiation phase. At that time, a Th2 profile was confirmed by expression of both the Th2- specific transcription factor GATA-3 and the chemokine receptor CCR4 and by suppression of the Thl cytokine IFNγ/IP-10 throughout the irradiation protocol. After 6 mo, despite the 2-fold reduction of iNOS and MCP-1 levels, the Th2 profile persisted, as shown by a 50% reduction in the expression of the Thl transcription factor T-bet, the chemokine receptor CCXCR3, and the IFNγ/ STAT1 pathway. At the same time-point, the immunosuppressive IL-10/STAT3 pathway, known to regulate the Th1/Th2 balance, was expressed, in irradiated rats, at approximately half its level as compared to controls.This suppression was associated with an overexpression of SOCS3, which inhibits the feedback of the Thl polarization and regulates IL-10 production. CONCLUSION： Colorectal irradiation induces Th2 polarization, defective IL-10/STAT3 pathway activation and SOCS3 overexpression. These changes, in turn, maintain a immunological imbalance that persists in the long term.
文摘In order to investigate the effects of interleukin-18 （IL-18） on airway inflammation and the Th1/Th2 cytokine balance in guinea pig asthmatic model as well as its possible mechanisms, the asthmatic model was established by intraperitoneal injection of ovalbumin （OVA） and aerosol challenges into guinea pigs, and 30 treated animals were randomly divided into three groups of 10 animals in each groups, in which group A served as the asthmatic model, group B as the controls and group C as the group treated with IL-18. The counting and categorization of the inflammatory cells in bronchoalveolar lavage fluid （BALF） were performed by using light microscopy, and the contents of cytokines （ IFN-γ, IL- 2, IL-4 and IL-5） were assayed by means of the ELISA kit. The experimental results showed that the numbers of eosinophils （ESO） in BALF of group A, B and C were （97.70 ± 58.03） × 10^6/L, （11.68 × 9.95） × 10^6/L and （28.62 ± 10.46） × 10^6/L, respectively, in which the number of eosinophils in group A was significantly higher than those of group B and C. Also, the number of neutrophils in BALF of group A was even higher than those in group B and C. In addition, the contents of IFN-7 and IL-2 in group A were lower than those in group B and C, but the contents of IL-4 as well as IL-5 were rather higher than those in group B and C. It is evident from the above observations that IL-18 can effectively inhibit the asthmatic inflammatory cells in BALF with an imbalance of the Thl/Th2 cytokines, thus offer- ing the experimental basis for the clinical application of IL-18 in the prevention and treatment of asthma.
