In vivo expression of the interleukin 4 receptor alpha by astrocytes in epilepsy cerebral cortex

We reported previously that non-neoplastic astrocytes (derived from brain tissues of patients with epilepsy) expressed interleukin 4 receptor alpha (IL-4R alpha) and responded to interleukin 4 (IL-4) in culture. To determine whether reactivity of cultured astrocytes was relevant to primary tissue, we investigated IL-4R alpha expression in specimens of non-neoplastic cerebral cortex removed for surgical treatment of intractable epilepsy compared to specimens of glial tumours, which have been reported to contain IL-4R alpha. Freshly frozen tissues from eight cases (four epilepsy, four malignant astrocytoma) were evaluated for IL-4R alpha expression by reverse-transcriptase polymerase chain reaction (RT-PCR), Southern blotting, and double-labelled immunohistochemistry with antibodies to IL-4R alpha and glial fibrillary acidic protein (GFAP), IL-4R alpha mRNA was detectable in both non-neoplastic and neoplastic tissues, whereas interleukin 2 receptor gamma chain (IL-2R gammac) mRNA was not found. By immunohistochemistry IL-4R alpha protein co-localized to cells displaying GFAP and astrocytic morphology in epilepsy tissues. As anticipated, IL-4Ra was detectable in astrocytoma, but, surprisingly, was also observed in GFAP-positive, non-neoplastic "reactive" astrocytes adjacent to tumour. Results are consistent with the concept that non-neoplastic epilepsy astrocytes express IL-4R alpha in situ, thus confirming in vitro studies and implying IL-4 sensitivity in vivo. (C) 2000 Academic Press.