The interleukin-1beta (IL1beta) and interleukin-6 (IL6) have pro-inflammatory and neuroprotective functions and are elevated in many diseases of the brain. Here, mechanisms and effects of IL1beta and IL6 on neuronal survival after excitatory stimulation were investigated in vitro. IL6 upregulated the expression of the neuroprotective acidic fibroblast growth factor (aFGF) and reduced the glutamate-induced cytotoxicity. IL1beta treatment amplified the excitotoxic effects after 24 h, but longer treatment with IL1beta stimulated the neuronal release of IL6 resulting in increased levels of aFGF and a decreased excitotoxicity. These data suggest that (1) IL6 exerts protective functions by upregulating the expression of aFGF and (2) the IL6/IL1beta balance in the brain may regulate neuronal survival during neuropathological processes.