Preventive effect of G-CSF on acute lung injury via alveolar macrophage regulation

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• 作者：Takeshi Yamaguchi ; MD^a ; Yoshihiro Miyata ; MD ; PhD^b ; ^{ymiyata@hiroshima-u.ac.jp} ; Keisuke Hayamizu ; MD ; PhD^c ; Jun Hashizume ; MD^a ; Tomio Matsumoto ; MD^a ; Hirotaka Tashiro ; MD ; PhD^a ; Hideki Ohdan ; MD ; PhD^a
• 关键词：Granulocyte colony-stimulating factor ; Acute lung injury ; Acute respiratory distress syndrome ; Tumor necrosis factor-¦Á ; Interleukin-1¦Â
• 刊名：Journal of Surgical Research
• 出版年：2012
• 出版时间：November, 2012
• 年：2012
• 卷：178
• 期：1
• 页码：378-384
• 全文大小：1548 K

文摘

Background

Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) are devastating clinical syndromes associated with a high mortality rate. We examined the preventive effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in a mouse ALI/ARDS model induced by lipopolysaccharide (LPS).

Materials and methods

Mice were injected with LPS (10-20 mg/kg) with or without rhG-CSF pretreatment (250 mg/kg/d). Survival rate, cytokine mRNA expression, and pathologic findings were examined.

Results

The 96-h survival rate of the control group was 20 % . Survival was significantly increased to 80 % in rhG-CSF-treated animals. LPS-induced destruction of the alveolar structure was not observed in the rhG-CSF group. Pretreatment with rhG-CSF led to significantly lower mRNA expression of TNF-¦Á and IL-1¦Â in the lung 24 h after LPS administration and significantly higher IL-10 expression 96 h after LPS administration. Immunohistochemical analysis revealed that treatment with rhG-CSF also prevented the up-regulation of TNF-¦Á and IL-1¦Â protein expression in alveolar macrophages.

Conclusion

Treatment with rhG-CSF prevents the development of ALI/ARDS induced by LPS by affecting the production of pro- and anti-inflammatory cytokines and may be promising in clinical applications.