Mechanisms of interleukin-6 synthesis and release induced by interleukin-1 and cell depolarisation in neurones

Cytokines are important mediators of the immune response to infection and injury and are produced mainly by lymphocytes or monocytes. Many aspects of the acute phase response are mediated by the actions of cytokines such as interleukin (IL)-1 and IL-6 within the brain. IL-1-induced IL-6 expression in neuronal cells has been described previously, but the mechanisms of IL-6 transport and release remain unknown. We show here that IL-1 induces IL-6 gene and protein expression in mouse primary cortical neurones, but that the IL-6 protein is stored intracellularly in the perinuclear area. Depolarisation of IL-1-treated neurones caused the axonal transport and release of IL-6 into the extracellular compartment. The transport and release occurs via an active mechanism (blocked by colchicine) through the Golgi apparatus, but not secretogranin-II vesicles. These results reveal a neuronal-specific mechanism of IL-6 synthesis, transport and release in response to IL-1 and cell depolarisation.