CYTOKINE EXPRESSION IN RADIATION-INDUCED DELAYED CEREBRAL INJURY

RADIATION-INDUCED DELAYED brain injury is a well-documented complicati on of both standard external beam radiation (teletherapy) and intersti tial brachytherapy; however, the cause of this damage has not been det ermined. Cytokines and growth factors are important regulatory protein s controlling the growth and differentiation of normal and malignant g lial cells, which have been implicated in the tissue response to radia tion injury. Six snap-frozen brain biopsies showing radiation injury w ere obtained from four patients harboring malignant gliomas who underw ent either postoperative external beam and/or stereotactic interstitia l brachytherapy at standard dosages. The specimens showed variable amo unts of gliosis, tissue necrosis, calcification, inflammation, and vas cular proliferation and hyalinization. Frozen tissue sections were exa mined for the presence of infiltrating lymphocytes, macrophages, cytok ines, and ether immunoregulatory molecules by the use of a panel of sp ecific monoclonal and polyclonal antibodies. All specimens showed diff use T cell infiltration with both CD4(+) and CD8(+) cells. Infiltratin g activated macrophages (CD11c(+), HLA-DR(+)) were prominent in five o f six cases. Tumor necrosis factor-alpha and interleukin-6 immunoreact ivity was prominent in four of six cases and was predominately localiz ed to macrophages. Transforming growth factor-beta astrocytic and macr ophage immunoreactivity was present at moderate levels in all cases. T his study suggests that in radiation necrosis, interleukin-1 alpha, tu mor necrosis factor-alpha, and interleukin-6 are expressed, predominat ely by infiltrating macrophages.