Cytokine expression in radiation-induced delayed cerebral injury.
Radiation-induced delayed brain injury is a well-documented complication of both standard external beam radiation (teletherapy) and interstitial brachytherapy; however, the cause of this damage has not been determined. Cytokines and growth factors are important regulatory proteins controlling the growth and differentiation of normal and malignant glial cells, which have been implicated in the tissue response to radiation injury. Six snap-frozen brain biopsies showing radiation injury were obtained from four patients harboring malignant gliomas who underwent either postoperative external beam and/or stereotactic interstitial brachytherapy at standard dosages. The specimens showed variable amounts of gliosis, tissue necrosis, calcification, inflammation, and vascular proliferation and hyalinization. Frozen tissue sections were examined for the presence of infiltrating lymphocytes, macrophages, cytokines, and other immunoregulatory molecules by the use of a panel of specific monoclonal and polyclonal antibodies. All specimens showed diffuse T cell infiltration with both CD4+ and CD8+ cells. Infiltrating activated macrophages (CD11c+, HLA-DR+) were prominent in five of six cases. Tumor necrosis factor-alpha and interleukin-6 immunoreactivity was prominent in four of six cases and was predominately localized to macrophages. Transforming growth factor-beta astrocytic and macrophage immunoreactivity was present at moderate levels in all cases. This study suggests that in radiation necrosis, interleukin-1 alpha, tumor necrosis factor-alpha, and interleukin-6 are expressed, predominately by infiltrating macrophages.
Department of Neurological Surgery, University of Southern California School of Medicine, Los Angeles.
S A
SA
Kureshi
F M
FM
Hofman
J H
JH
Schneider
L S
LS
Chin
M L
ML
Apuzzo
D R
DR
Hinton
D000328:Adult; D000368:Aged; D001918:Brachytherapy; D001921:Brain / Q000276:immunology / Q000473:pathology / Q000528:radiation effects*; D001932:Brain Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D016207:Cytokines / Q000378:metabolism*; D005910:Glioma / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D007124:Immunoenzyme Techniques; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000378:metabolism*; D011832:Radiation Injuries / Q000276:immunology* / Q000473:pathology; D011879:Radiotherapy Dosage; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D009414:Nerve Growth Factors; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha