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

In order to study the role of interleukin-1beta (IL-1 beta) in homeostasis. hypoxia and recovery of neuronal cells, we studied the expression and rele ase of tumor necrosis factor-alpha (TNF-alpha) and nerve growth factor (NGF ), in relation to the presence or absence of this cytokine in culture mediu m. Moreover, we evaluated cell mortality in the same conditions. For this a im, we used untreated and IL-1 beta pre-immunoneutralized hippocampal neuro nal cultures exposed to mild hypoxic stress and left to reoxygenate. Semiqu antitative reverse-transciptase-polymerase chain reaction (RT-PCR) and enzy me-linked immunosorbent assay (ELISA) determined gene expression and protei n levels. Mild hypoxic stress provokes a decrease in both the expression an d release of TNF-alpha and NGF. IL-1 beta neutralization results in an inve rsion of this pattern since treated hypoxic cultures exhibited an increase of both expression and release of NGF. fn pretreated hypoxic cells the incr eased expression of TNF-alpha was not followed by a rise in release. Reoxyg enation reversed the observed effects in both cultures and the levels of cy tokine expression and release were approaching control values. Our data sho w that in physiological conditions IL-1 beta may have a neuroprotective act ion through positive modulation of NGF. Contrary to that, in presence of in sult, IL-1 beta may have an opposite role, since neutralization provoked an increase of expression and release of NGF. In addition, we demonstrated th at neuronal cells are biochemically capable, not only of maintaining and re covering the homeostasis, but also of activating the appropriate response t o insult. IL-1 beta may have a pivotal role in this mechanism through the m odulation of NGF and to a lesser degree of TNF-alpha. (C) 2000 Elsevier Sci ence B.V. All rights reserved.