EXPRESSION AND RELEASE OF INTERLEUKIN-1 BY HUMAN GLIOBLASTOMA CELLS-INVITRO AND INVIVO

The present study demonstrates interleukin-1 (IL-1) production by human glioblastoma cells both in vitro and in vivo. The presence of IL-1alpha and IL-1beta transcripts was analyzed in 4 cell lines. IL-1alpha mRNA was expressed constitutively in one cell line whereas constitutive IL-1beta mRNA could not be detected in any of the cell lines. IL-1alpha transcripts could be induced with phorbol myristate acetate (PMA) or PMA plus lipopolysaccharide (LPS) in 2 of 4 cell lines and IL-1beta mRNA in 2 of 4 cell lines. Culture fluid from these cell lines was tested for the presence of IL-1 using a specific radio-immuno-assay for either IL-1alpha or IL-1beta. In agreement with the results on RNA, one of 4 cell fines was found to constitutively produce IL-1alpha but not IL-1beta. After treatment with PMA and LPS, IL-1alpha was detected in the culture fluid from two other lines and IL-1beta in the medium from three lines. That the IL-1 produced by these cell lines was biologically active was confirmed in a two step thymocyte proliferation assay. IL-1 like activity was detected in all samples that were positive in the radio-immuno-assay. Finally, immunohistological analysis on fresh frozen tumour sections provided evidence for IL-1 production by glioblastoma cells in vivo. Fourteen out of 28 glioblastomas were stained with an anti-IL-1alpha a monoclonal antibody while none of them was stained with an anti-IL-1beta antibody.