Effects of interferons and hydrogen peroxide on CA3 pyramidal cells in rat hippocampal slice cultures

In viral diseases of the CNS, both interferon-alpha/beta and interferon-gamma are produced intrathecally. At least some of the neurological symptoms associated with these diseases may be due to the effects of these cytokines. We have studied the actions of interferons on CA3 pyramidal cells in hippocampal slice cultures. Bath application of interferon-alpha/beta and interferon-gamma produced an excitatory effect on CA3 pyramidal cells and a decrease in evoked inhibitory postsynaptic potential amplitude, eventually leading to epileptiform bursting. These effects were slow in onset (several minutes), suggesting an indirect mechanism of action. Several lines of evidence suggest that the actions of interferons on pyramidal cells may at least in part be mediated by reactive oxygen intermediates, known to be released from non-neuronal cells: the effects of interferon on CA3 pyramidal cells were blocked by the free radical scavengers catalase and superoxide dismutase. Hydrogen peroxide reduced evoked inhibitory synaptic transmission, eventually leading to epileptiform bursting, thus mimicking several of the effects of interferons on pyramidal cells.