TRANSFER OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR GENE TO RAT LUNG INDUCES EOSINOPHILIA, MONOCYTOSIS, AND FIBROTIC REACTIONS

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotr opic cytokine whose expression is increased in numerous respiratory di seases, particularly in asthma. However, the role of GM-CSF in the pat hogenesis of these conditions in vivo remains unclear. Here, we report the functional activities of GM-CSF highly expressed in rat lung afte r intrapulmonary transfer of the gene coding for murine GM-CSF by usin g an adenoviral vector. This high, transient expression of GM-CSF led to the sustained but self-limiting accumulation of eosinophils and mac rophages associated with tissue injury in the lung followed by varying degrees of irreversible fibrotic reactions observed in later stages. These results suggest that GM-CSF plays a previously unrealized role i n the development of respiratory conditions characterized by eosinophi lia, granuloma and/or fibrosis and provide the rationale for targeting this molecule in these diseases.