Irradiation induces increased production of haemopoietic and proinflammatory cytokines in the mouse lung

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Abstract
Purpose : To investigate cytokine expression following irradiation of mice, predominantly in lung tissue but also in selected other tissues. Materials and methods : Mice of strain ICR were whole-body (unilaterally) exposed to 3-20 Gy of 60 Co γ-rays. Colony-stimulating activity (CSA) of lung-conditioned media (LCM), and also other non-haemopoietic and haemopoietic organs, and blood serum of mice was assayed using a GM-CFC bioassay. The production of GM-CSF, IL-6 and TNF- α protein in LCM and sera was determined by an ELISA method. Results : Greatest CSA was detected in conditioned media from the lungs and was induced in a dose- and time-dependent fashion, peaking at 3-9 days after irradiation with a lethal dose of 9 Gy. Conditioned medium prepared from lungs that had been irradiated with a dose of 9 Gy in vitro did not exhibit an increase in CSA. However, whereas the lung-conditioned medium from irradiated mice was found to produce CSA, sera from normal or irradiated mice did not lead to this effect. A significant increase in CSA in sera was observed in the presence of a suboptimal concentration of IL-3, implying that they comprise the co-stimulatory activity (CoSA). The results showed that radiation exposure increased GM-CSF and TNF- α protein levels but did not affect IL-6 production in LCM. In contrast, IL-6 and TNF- α protein levels in serum were increased after irradiation but no GM-CSF production could be detected. Conclusion : Whole-body irradiation enhances CSA in lungs as well as in other haemopoietic and non-haemopoietic organs. The increase of CSA correlates with increased levels of haemopoietic and proinflammatory cytokines in lung.

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