Glioblastoma is the most common and uncompromising primary brain tumour and is characterized by a dismal prognosis despite aggressive treatment regimens. At the cellular level, these tumours are composed of a mixture of neoplastic cells and non-neoplastic cells, including tumour-associated macrophages and endothelial cells. Cerebral oedema is a near-universal occurrence in patients afflicted with
glioblastoma and it is almost exclusively managed with the
corticosteroid dexamethasone despite significant drawbacks associated with its use. Here, we demonstrate that
dexamethasone blocks
interleukin-1 production in both bone marrow-derived and brain resident macrophage populations following stimulation with
lipopolysaccharide and
interferon gamma. Additionally,
dexamethasone is shown to inhibit downstream effectors of
interleukin-1 signalling in both macrophage populations. Co-culture of bone marrow-derived macrophages with organotypic tumour slices results in an upregulation of
interleukin-1 cytokines, an effect that is absent in co-cultured microglia. Genetic ablation of
interleukin-1 ligands or receptor in mice bearing RCAS/tv-a-induced
platelet-derived growth factor B-overexpressing
glioblastoma results in reduced oedema and partial restoration of the integrity of the blood-brain barrier, respectively; similar to results obtained with
vascular endothelial growth factor neutralization. We establish that tumours from
dexamethasone-treated mice exhibit reduced infiltration of cells of the myeloid and lymphoid compartments, an effect that should be considered during clinical trials for
immunotherapy in
glioblastoma patients. Additionally, we emphasize that caution should be used when immune profiling and single-cell
RNA sequencing data are interpreted from fresh
glioblastoma patient samples, as nearly all patients receive
dexamethasone after diagnosis. Collectively, this evidence suggests that
interleukin-1 signalling inhibition and
dexamethasone treatment share therapeutic efficacies and establishes
interleukin-1 signalling as an attractive and specific therapeutic target for the management of
glioblastoma-associated cerebral oedema.