Malignant glioblastomas are characterized by infi ltration of tumour tissue with brain macrophages that contribute to tumour progression through release a variety of growth factors, cytokines/ chemokines supporting tumor growth, invasion and the immune system evasion. Thus targeting of cytokine production, infi ltration and activation of macrophages may be a novel antitumor strategy. In the present study, we investigated an effectiveness and molecular mechanisms mediating antitumor effects of CsA in the murine glioma model. EGFP-GL261 glioma cells were injected into the striatum of C57BL/6 mice and tumor-bearing mice received CsA (2 or 10 mg/kg/i.p.) every 2 days from 2nd or 8th day after implantation. CsA-treated mice had signifi cantly smaller tumors than control mice. When the treatment was postponed to 8th day, only the higher dose of CsA was effective. CsA-treated mice showed a diminished number of tumor-infi ltrating, amoeboid brain macrophages. TUNEL staining revealed a DNA fragmentation mostly within infi ltrating macrophages after CsA treatment. At concentrations <10 μM CsA did not affect proliferation or viability of cultured glioma cells. Elevated IL-10 and GM-CSF levels were found in tumor-bearing hemisphere in comparison to naive controls and CsA treatment reduced signifi cantly cytokine levels. Our fi ndings demonstrate that CsA-induced decrease of cytokine production, infi ltration and activation of macrophages results in reduction of glioma growth and progression.
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