In this study, we investigated the capacity of murine cortical neurons to express interleukin-6 (IL-6) mRNA and protein in culture. Using in situ hybridization techniques, IL-6 mRNA was localized to neuronal cells in these cultures. Moreover, IL-6 mRNA expression as measured by in situ and PCR was shown to be upregulated by the proinflammatory cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). This was consistent with the dose and time-dependent increases in IL-6 secreted protein observed from cultures stimulated with IL-1 beta and TNF-alpha. Taken together, the data suggest that neurons are capable of participating more directly in the CNS cytokine network than previously thought and may play an important role in the inflammatory response activities in the brain.