Interleukin 1-beta modulates the effects of Hypoxia in neuronal culture

In order to study the role of interleukin-1beta (IL-1b) in homeostasis, hypoxia and recovery of neuronal cells, we studied the expression and release of tumor necrosis factor-alpha (TNF-a) and nerve growth factor (NGF), in relation to the presence or absence of this cytokine in culture medium. Moreover, we evaluated cell mortality in the same conditions. For this aim, we used untreated and IL-1b pre-immunoneutralized hippocampal neuronal cultures exposed to mild hypoxic stress and left to reoxygenate. Semiquantitative reverse-transciptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) determined gene expression and protein levels. Mild hypoxic stress provokes a decrease in both the expression and release of TNF-a and NGF. IL-1b neutralization results in an inversion of this pattern since treated hypoxic cultures exhibited an increase of both expression and release of NGF. In pretreated hypoxic cells the increased expression of TNF-a was not followed by a rise in release. Reoxygenation reversed the observed effects in both cultures and the levels of cytokine expression and release were approaching control values. Our data show that in physiological conditions IL-1b may have a neuroprotective action through positive modulation of NGF. Contrary to that, in presence of insult, IL-1b may have an opposite role, since neutralization provoked an increase of expression and release of NGF. In addition, we demonstrated that neuronal cells are biochemically capable, not only of maintaining and recovering the homeostasis, but also of activating the appropriate response to insult. IL-1b may have a pivotal role in this mechanism through the modulation of NGF and to a lesser degree of TNF-a.