Interferon entry through the blood-brain barrier in glioma and its effect on lipoxygenase activity

This study evaluates cerebral entry of mouse interferon alpha/beta (MuIFN alpha/beta) or mouse interferon gamma (MuIFN-gamma) following continuous (3 day), subcutaneous infusion of normal or glioma bearing mice. The intracerebral C57BL/6 mouse glioma-26 (G-26) model was used at days 10-14 post tumor implant, the advanced stage of glioma progression as defined by histology and the median survival time (27 +/- 3.8 days). The infusion of horseradish peroxidase (HRP) in vivo at day 10 or 11 post glioma implant showed strong staining in the tumor bed indicating compromised blood-brain barrier (BBB). In addition, histochemistry with Bandeiraea simplicifolia isolectin B4 demonstrated the accumulation and/or activation of macrophage/microglia. The 3 day infusion of mice (day 11-14 post tumor implant) via subcutaneous (sc) osmotic micro-pumps with MuIFN alpha/beta (8x10(5) - 1.7x10(6) international units [IU]/ml) or with recombinant mouse interferon gamma (rMuIFN-gamma) (1x10(6) IU/ml) resulted in a low but detectable (1-5 IU/ml) cerebral level of IFN. The IFN levels in the blood (20-40 IU/ml) and brain, measured by assay of inhibition of viral cytopathic effect (CPE) or ELISA assay for MuIFN-gamma, showed no difference between normal and glioma bearing mice. The lipoxygenase (LO) activity (dioxygenase) of glioma tissue and contralateral control was evaluated in non-treated and MuIFN alpha/beta continuously (3 day) treated mice. The LO activity in glioma tissue was significantly higher (p < 0.05) than the contralateral control in non-treated mice. However, following sc MuIFN alpha/beta infusion the LO activity of glioma decreased to control level.