Interferon modulates neuronal activity recorded from the hypothalamus, thalamus, hippocampus, amygdala and the somatosensory cortex.

Neuromodulators interact with classically defined neurotransmitters to regulate a variety of biological processes. The aim of the present study was to study whether interferon-alpha (IFN) can be considered as a neuromodulator. Single cell recordings from five CNS structures were recorded before and following three different routes of IFN administration in Sprague-Dawley rats to substantiate that IFN is a neuromodulator. IFN modulated the majority of the hypothalamic (70%), amygdala (76%), hippocampus (75%) and cortical (82%) cells whether the route of administration was within the brain or given peripherally (i.v. or i.p.). The main difference among the three routes of IFN administration on the neuronal activity of these four CNS sites was the onset of the effect. However, the thalamic neurons responded differently. IFN injection within the brain modulated activity of 43% of thalamic neurons, but only 25% and 17% of the neurons when IFN was given i.v. or i.p., respectively. IFN, in general suppressed hypothalamic neuronal activity while accelerating neuronal activity in all the other studied CNS sites. In conclusion, IFN is an endogenous peptide synthesized and released both peripherally and centrally, with the same effects on neuronal activity whether it is given systemically or locally within the brain. This suggests that IFN can be considered as a neuromodulator.