Rapid induction of cytokine gene expression in the lung after single and fractionated doses of radiation

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Abstract
To investigate cytokine gene expression in the lung after single and fractionated doses of radiation, and to investigate the effect of steroids and the genetic background. Expression of cytokine genes (mTNF-alpha, mIL-1alpha, mIL-1beta, mIL-2, mIL-3, mIL-4, mIL-5, mIL-6, mIFN-gamma) in the lungs of C3H/HeJ and C57BL/6J mice was measured by RNase protection assay at different times after various doses of radiation. The effects of dexamethasone and fractionated radiation treatment on gene expression were also studied. IL-1beta was the major cytokine induced in the lungs of C3H/HeJ mice within the first day after thoracic irradiation. Radiation doses as low as 1 Gy were effective. Responses to 20 Gy irradiation peaked within 4-8h and subsided by 24 h. With the exception of IL-1alpha and TNF-alpha, the other cytokines that were investigated had undetectable pre-treatment mRNA levels and were not radiation inducible. Similar responses were seen in C57BL/6J mice, although TNF-alpha was induced and there were some quantitative differences. Pre-treatment of C3H/HeJ mice with dexamethasone reduced basal and induced IL-1 levels, but complete inhibition was not achieved. Dexamethasone was also effective if given immediately after irradiation. Fractionated daily doses of radiation (4 Gy/day) helped to maintain cytokine gene expression for a longer period. Inflammatory genes are rapidly induced in the lung by irradiation. This response cannot be readily abolished by steroid pre-treatment. Fractionated treatment schedules help to perpetuate the response.

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