Modified immunoregulation associated with interferon-gamma treatment of rat glioma

Little is known about modulation by cytokines of major histocompatibility complex (MHC) antigen expression on intracranial tumors in vivo. The ability of cytokines to up-regulate MHC class-1 (MHC-1) antigen expression was investigated first in vitro using three rat glioma cell lines. Immunohistochemistry showed that incubation with recombinant rat interferon-gamma (rrIFN-gamma) increased MHC-1 antigen expression in RG2, C6, and 9L cell lines. Flow cytometric analysis revealed different baseline levels of MHC-1 antigen expression in each line (RG2 lowest, C6 highest), and that these levels increased in all lines after stimulation with 100 U ml(-1) or more of rrIFN-gamma. The antitumor effect of rrIFN-gamma in vivo was evaluated by assessing survival of rats with implanted intracerebral RG2 gliomas after intracarotid infusion of rrIFN-gamma. A high dose of rrIFN-gamma (2.4 x 10(5) U kg(-1)) significantly increased the survival, compared to control (p < 0.02). Intracarotid pre-treatment with the bradykinin analogue RMP-7 did not further increase survival. Immunohistochemical staining of tumor sections after in vivo rrIFN-gamma, infusion showed no clear increase in MHC-1 antigen expression on tumor cells but increased staining for ED2 antigen within tumor tissue, presumably from perivascular cells with MHC class-2 antigen.