Tuberc Respir Dis.  2009 Jul;67(1):14-20.

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

• Choi YJ
• Rho JK
• Jang WS
• Lee SJ
• Lee SS
• Koh JS
• Kim JY
• Kim HR
• Kim CH
• Lee JC

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.

Keyword

Radiation; Lung injury; Cytokines

MeSH Terms

Animals
Cytokines
Enzyme-Linked Immunosorbent Assay
Fibrosis
HMGB1 Protein
Humans
Lung
Lung Injury
Mice
Thorax
Tumor Necrosis Factor-alpha
Cytokines
HMGB1 Protein
Tumor Necrosis Factor-alpha

Figure

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  Figure 1 Histologic changes of lung parenchyma at 4 h (A), 2 wk (B), and 8 wk (C) after 20 Gy irradiation. (A) Peri-vascular edema and an increased interstitial cellularity due to exudative neutrophilic infiltration in interstitial vascular spaces were found. (B) Lymphocytic collectons were noted in the interstitium with no evidence of fibrosis 2 weeks after irradiation. (C) Alveolar spaces were distorted by mild fibrosis and inflammatory infiltration was persistent (H&E stain, ×200).

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  Figure 2 Biphasic increase of cytokines in lung after irradiation. The level of TNF-α (A), MIP-2 (B) and IL-1β (C) in ling homogenates was determined by ELISA kits at the indicated time after irradiation. Each experimental group consisted of 3 mice.

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  Figure 3 The expression level of HMGB1 did not change in lung parenchyma after irradiation. The amount of HMGB1 in the lung was examined by Western blot analysis (A). The expression level of HMGB1 was also evaluated by ELISA kits in lung homogenate (B) and serum (C) at the indicated times after irradiation. Each experimental group consisted of 3 mice.

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