Background: The detrimental and protective effects of interleukin 1(3 (IL-1(3) have been reported. We have previously shown that the periods of IL-1(3 elevation is related to its dual effects. However, the effects of different IL- 1(3 concentrations on neuropathological processes are unclear. Studies have demonstrated that mature brain- derived neurotrophic factor (mBDNF) and its precursor (proBDNF) have opposing functions in neuronal survival. We previously showed that mBDNF is involved in IL-1(3-mediated neuropathology. Here, we investigated whether different IL-1(3 concentrations differentially affect mBDNF and proBDNF, determining their beneficial or harmful effects. Methods: HT22 cells were cultured and exposed to various IL-1(3 concentrations for different durations. HT22 cell viability and the expression of mBDNF, proBDNF and their receptors were evaluated by a Cell Counting Kit-8 (CCK-8) assay and western blot. Results: Compared with untreated cells, a significant reduction in cell viability was observed after exposure to high IL-1(3 concentrations for more than 24 h. Increased expression of proBDNF and its receptor p75NTR and decreased expression of mBDNF and its receptor TrkB, as well as decreased furin and PC1/3 (which promote the cleavage of proBDNF to mBDNF) expression, were detected. In contrast, low IL-1(3 concentrations increased cell viability, but a significant effect was observed only at an optimal concentration; in contrast to our predictions, low IL-1(3 concentrations did not induce significant alterations in mBDNF and proBDNF expression levels, but rather, low concentrations significantly increased the mBDNF/proBDNF ratio. Conclusions: These results demonstrated that changes induced by low (neuroprotection) and high (neurodegeneration) IL-1(3 concentrations were oriented in different directions. These dual effects occur partly through the modulation of mBDNF signaling.