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What is the mechanism of the chronic radiation enteritis?

The use of radiation therapy to treat cancer inevitably involves exposure of normal tissues. Although the benefits of this treatment have been well established, a number of patients experience distressing complications as a result injury to normal tissue These side effects related to inflammatory process cause discomfort and decreases the therapeutic benefit by increasing the overall treatment time.

A research article to be published on December 14, 2008 in the World Journal of Gastroenterology addresses the question. The research led by Dr. Christine Linard and her colleagues from the Institute for Radioprotection and Nuclear safety (IRSN) in France used experimentally a fractionated colorectal irradiation model to demonstrate an immune imbalance during the radiotherapy protocol and persisting in long term.

They found that without causing histological damage, fractionated radiation induced elevated expression of IL-1beta, TNF alpha, 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 Th1 cytokine IFN gamma/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 Th1 transcription factor T-bet, the chemokine receptor CCXCR3, and the IFNgamma /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 Th1 polarization and regulates IL-10 production.

The major result is that the immunity alteration persisted in long term, i.e. after the end of the radiotherapy protocol. These data raise the question whether the post-irradiation Th2 polarization in the intestine (both acute and delayed) may result from changes in the dynamics of lymphocyte recirculation.


Contact: Lai-Fu Li
World Journal of Gastroenterology

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