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

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-α and IL-1β 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-α and IL-1β 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.