Interferon-alpha reduced inflammatory effects of filgrastim (G-CSF) in the liver of Syrian mice

Introduction: granulocyte colony-stimulating factor (G-CSF) has been widely used for the treatment of chemotherapy-induced neutropenia. One of the major sideeffects of interferon-α (IFN-α) therapy is neutropenia. Previous studies have confirmed the beneficial effects of co-administration of G-CSF and IFN-α on neutropenia in patients infected with hepatitis C. In this study for the first time, the effects of co-administration of type I IFNs and G-CSF on liver and liver enzymes investigated. Methods: forty-two mice (male, eight weeks) were randomly divided into six groups of seven: distilled water, G-CSF (200μg/kg), IFN-α (200μg/kg), IFN-β (200μg/kg), IFN-α+G-CSF and IFN-β+G-CSF. After 28 days, blood was taken from the heart of each mouse and histological changes in the liver and liver enzymes including aspartate transaminase (AST) and alanine transaminase (ALT), as well as bilirubin, were measured. Results: Surprisingly, in most cases, the G-CSF and type one IFNs alone or simultaneously reduced the levels of AST and bilirubin. The levels of ALT induced by IFN-α, the addition of G-CSF to IFN-α reduced the level of this liver enzyme. G-CSF induced cell infiltrations into the liver tissue, addition of IFN-α but not IFN-β to G-CSF obviously reduced the cell infiltration into the liver. Conclusion: Since the changes in liver enzymes and bilirubin were not at harmful levels, and the administration of IFN-α to G-CSF reduced the cell infiltrations into the liver, our results suggested that co-administration of type I IFNs and G-CSF had no harmful effects on liver histology and functions.