Mizutani, N., Fujikura, Y., Wang, Y-H., Tamechika, M., Tokuda, N., Sawada, T. and Fukumoto, T. Inflammatory and Anti-inflammatory Cytokines Regulate the Recovery from Sublethal X Irradiation in Rat Thymus. Radiat. Res. 157, 281 – 289 (2002).
We investigated the regeneration of rat thymus after sublethal X irradiation (6 Gy). The number of thymocytes was much lower on day 3 after irradiation, and many apoptotic cells were observed. However, by day 5, there had been a rapid proliferation of thymocytes. Since cytokines are considered to be important regulatory factors in postirradiation recovery, we performed in vivo cytokine assays using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and found serial changes in the cytokine message. The messenger RNA (mRNA) expression of the pro-inflammatory cytokines interleukin 1 beta (Il1b), Il6 and tumor necrosis factor alpha (Tnf) was higher than normal on day 3, lower on day 5, and higher again on day 7. In particular, Tnf was completely absent on day 5 and was expressed again on day 7. Of the anti-inflammatory cytokines Il4, transforming growth factor beta (Tgfb) and Il10, only the Il10 message changed substantially. Il10 expression was very high on day 5 but was completely absent on day 7. Thus the Tnf and Il10 messages were expressed alternately. The changes in the distribution of macrophages detected by the immunohistochemical analysis may be related to the changes in the cytokines. Analysis of cytokine messages in the regenerating thymus in vivo may provide new insights into potential therapies for radiation-induced damage.