Expression of interleukin-16 by tumor-associated macrophages/activated microglia in high-grade astrocytic brain tumors

Abstract

Introduction: Macrophages/microglial cells are considered as immune cells in the central nervous system. Interleukin (IL)-16 is a proinflammatory cytokine produced by activated monocytic cells.

Materials and methods: Expression of IL-16 was analyzed by immunohistochemistry in human astrocytic brain tumors and the rat C6 glioblastoma tumor model. IL-16 was detected in both human astrocytic brain tumors and rat C6 glioma.

Results: Compared with human control brains, a significant increase in the percentages of parenchymal IL-16+ macrophages/microglia was observed already in grade II astrocytomas, indicating that IL-16+ immunostaining could be a descriptor of a macrophage/microglia subset in astrocytic brain tumors. A further increase was observed at the transition from grade II to III astrocytomas. This increase in IL-16 immunoreactivity correlated with WHO grades of human astrocytic brain tumors.

Conclusions: Therefore, IL-16 might be a so far unknown factor in the regulation of the local inflammatory milieu of human and experimental astrocytomas.

Fig. 1

Single immunohistochemical staining of IL-16 in control human brain (A), WHO Grade II fibrillary astrocytoma (B), WHO Grade III anaplastic astrocytoma (C), and WHO Grade IV glioblastoma (D). Arrows indicate IL-16⁺ cells. In the glioma, double-labelling of IL-16 (brown) with CD68 (blue) confirms that macrophages are labelled with antibody against IL-16 (E). Double-labelling of IL-16 (brown) with MHC-II (blue) (F). Double-labelling of IL-16 (brown) with CD4 (blue) (G). Double-labelling of IL-16 (brown) with CD3 (blue) (H). A–D: ×200; E–H: ×400.

Fig. 2

Statistical evaluation of the distributions of IL-16⁺ cells in parenchyma sections (A) and in perivascular areas (B) in astrocytomas of different malignancies. C — control brain; PRO — protoplasmatic astrocytoma (WHO grade II); FA — fibrillary astrocytoma (WHO grade II); ANA — anaplastic astrocytoma (WHO grade III); GBM — glioblastoma multiforme (WHO grade IV).

Fig. 3

Single-labelling of IL-16 in rat brain sections. In normal rat brain, IL-16 staining was hardly seen (A). In rats with implanted C6 glioma, IL-16⁺ cells were strikingly located in areas of tumor mass (B); in the tumor infiltration areas, IL-16⁺ cells were especially concentrated in perivascular areas (C). Double-staining of IL-16⁺ cells (brown) with ED1 (blue) in the tumor infiltration of C6 glioma revealed these cells as microglia/macrophages (arrows). A–C: ×200; D: ×400