Biphasic Increase of Pro-inflammatory Cytokines in Mice Lung after Irradiation / 결핵및호흡기질환

ABSTRACT

BACKGROUND: The pathophysiologic mechanisms of radiation-induced lung injury should be elucidated to enhance the therapeutic efficacy of radiotherapy and to manage patients exposed to serious radiation by accident. It has been suggested that pro-inflammatory cytokines play an important role in radiation-induced effect on the lung. This study was aimed to investigate changes in pro-inflammatory cytokines such as TNF-alpha, MIP-2, IL-1beta and HMGB1, a newly recognized inflammatory mediator. METHODS: The chests of BALB/c mice were selectively irradiated with single fraction of 20 Gy and then sacrificed at indicated times. Pathologic changes in the lung were examined after H&E staining. The expression level of pro-inflammatory cytokines was evaluated by ELISA kits in lung homogenate and in serum. RESULTS: Radiation induced inflammatory changes and mild fibrosis in lung. Biphasic increase of TNF-alpha and IL-1beta was found in lung homogenate at 4 hours and at 3 weeks after radiation. The elevation in the second phase tended to be more intense. However, there was no similar change in serum. MIP-2 level was slightly increased in lung homogenate at 4 hours, but not at 3 weeks. HMGB1 was increased at 3 weeks in serum while there was no significant change in lung homogenate. CONCLUSION: Radiation induced a biphasic increase in TNF-alpha and IL-1beta. The effective control of second phase cytokine elevation should contribute to preventing severe lung fibrosis caused by radiation.