Wiranowska M, Prockop L D, Naidu A K, Saporta S, Kori S, Kulkarni A P
Department of Neurology, College of Medicine, University of South Florida, Tampa 33612.
Anticancer Res. 1994 May-Jun;14(3A):1121-6.
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.
本研究评估了在正常小鼠或荷胶质瘤小鼠连续（3天）皮下输注后，小鼠α/β干扰素（MuIFNα/β）或小鼠γ干扰素（MuIFN-γ）进入脑内的情况。在肿瘤植入后10 - 14天使用脑内C57BL/6小鼠胶质瘤-26（G-26）模型，这是胶质瘤进展的晚期阶段，由组织学和中位生存时间（27±3.8天）定义。在胶质瘤植入后第10天或第11天体内输注辣根过氧化物酶（HRP），在肿瘤床显示出强烈染色，表明血脑屏障（BBB）受损。此外，用简单叶豆凝集素B4进行组织化学分析显示巨噬细胞/小胶质细胞的积累和/或激活。通过皮下（sc）渗透微型泵对小鼠（肿瘤植入后第11 - 14天）连续3天输注MuIFNα/β（8×10⁵ - 1.7×10⁶国际单位[IU]/ml）或重组小鼠γ干扰素（rMuIFN-γ）（1×10⁶IU/ml），导致脑内IFN水平较低但可检测到（1 - 5 IU/ml）。通过病毒细胞病变效应（CPE）抑制试验或MuIFN-γ的ELISA试验测量的血液（20 - 40 IU/ml）和脑内IFN水平，在正常小鼠和荷胶质瘤小鼠之间没有差异。在未治疗和连续（3天）接受MuIFNα/β治疗的小鼠中，评估了胶质瘤组织和对侧对照的脂氧合酶（LO）活性（双加氧酶）。在未治疗的小鼠中，胶质瘤组织中的LO活性显著高于对侧对照（p < 0.05）。然而，皮下输注MuIFNα/β后，胶质瘤的LO活性降至对照水平。
