Differential actions of IL-1 alpha and IL-1 beta in glial cells share common IL-1 signalling pathways

The cytokine interleukin (IL)-1 plays important roles in peripheral and central inflammation via the actions of two ligands IL-1 alpha and IL-1beta that bind to the IL-1 type I receptor (IL-1RI) and trigger identical responses. However, some recent evidence suggests that IL-1alpha and IL-1beta may have differential actions in the CNS. The aim of this study was to characterise the molecular mechanisms responsible for their differential actions in the brain. We show that, while IL-1alpha and IL-1beta induce identical IL-1 signalling pathways, IL-1beta is significantly more potent than IL-1alpha in stimulating IL-6 release in primary mixed glia. These data suggest that the differential effects of IL-1alpha and IL-1beta on glial cells are mediated by alternative pathways to the classical IL-1 signalling cascade.