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In Parkinson's disease (PD) chronic inflammation occurs in the substantia nigra (SNc) concurrently with dopaminergic neurodegeneration. In models of PD, microglial activation precedes neurodegeneration in the SNc, suggesting that the underlying pathogenesis involves a complex response in the nigrostriatal pathway, and that the innate immune system plays a significant role. We have investigated the neuroprotective effect of an adeno-associated viral type-2 (AAV2) vector containing the complementary DNA (cDNA) for human interleukin-10 (hIL-10) in the unilateral 6-hydroxydopamine (6-OHDA) rat model of PD. AAV2-hIL-10 reduced the 6-OHDA-induced loss of tyrosine hydroxylase (TH)-positive neurons in the SNc, and also reduced loss of striatal dopamine (DA). Pretreatment with AAV2-hIL-10 reduced glial activation in the SNc but did not attenuate striatal release of the inflammatory cytokine IL-1β …