Suppression of inflammation by dexamethasone prolongs adenoviral vector-mediated transgene expression in the facial nucleus of the rat

Abstract

Adenoviral vector directed gene transfer to rat facial motoneurons occurs efficiently following intra-parenchymal injection of relatively high dosages (≥10 7 pfu per injection) of a prototype first generation adenoviral vector. However, high level of transgene expression, as observed during the first week following administration of the adenoviral vector, declines during the second and third weeks and is associated with a local inflammatory response. In the present study rats were treated with dexamethasone to suppress the inflammatory response that occurs following administration of a first generation adenoviral vector and the effect of dexamethasone treatment on the duration of transgene expression was studied. Dexamethasone-treated rats displayed a reduced infiltration of macrophages and intra-parenchymal T-cells were not detectable at 14 days post-infusion of the viral vector. Transduced astrocytes persisted following treatment with dexamethasone, whereas only a few transduced motoneurons survived. In conclusion, suppression of inflammation by dexamethasone has a beneficial effect on the survival of transduced astroglial cells but exerts only moderate protection on transduced facial motoneurons.