Interleukin-10 protects against inflammation-mediated degeneration of dopaminergic neurons in substantia nigra

Contributions of central and systemic inflammation to the pathophysiology of Parkinson's disease

“…Pre-treatment of mesencephalic neuroglial cultures with IL-10 inhibited LPS-stimulated microglial activation and degeneration of dopaminergic neurons (Qian et al, 2006). Similar neuroprotective effects were observed in vivo after chronic infusion of IL-10 into the SNpc of rats that were challenged with LPS (Arimoto et al, 2006). More recently, gene therapy approaches have been developed to deliver IL-10 into the rat SNpc, and have proved effective in attenuating the neuronal loss and behavioural deficits in the 6-OHDA rat model of PD (Johnston et al, 2008).…”

Interleukin-10 endogenously expressed in microglia prevents lipopolysaccharide-induced neurodegeneration in the rat cerebral cortex in vivo

“…A recent study demonstrated that osmotic pump infusion of recombinant IL-10 protected LPSinduced dopaminergic neuronal cell death in the substantia nigra, by inhibiting microglial activation (Arimoto et al, 2007). Further, our study found that IL-10 was endogenously expressed in microglia, which in turn prevented LPS-induced neurodegeneration in the rat cerebral cortex in vivo, and that the time course of IL-10 expression paralleled those of the pro-inflammatory mediators IL-1β, TNF-α, and iNOS.…”

“…IL-10 is therefore considered to be an important anti-inflammatory modulator of glial activation, functioning to maintain a balance between pro-and anti-inflammatory cytokine levels in the CNS (Sawada et al, 1999). Moreover, two recent studies have shown that treatment with IL-10 inhibited LPS-induced degeneration of dopaminergic neurons either in culture, or in the substantia nigra, by preventing microglial activation (Qian et al, 2006;Arimoto et al, 2007). Collectively, these observations suggest that IL-10 produced by microglia counteracts brain inflammation, and that such production leads to neuronal survival.…”

Inflammation in Parkinson’s Disease: Causes and Consequences

“…Intranigral injection of LPS in rats has been shown to manifest Parkinsonism-like symptoms, such as the selective loss of DA neurons in the SN (Arimoto et al, 2006;Castano et al, 1998;Herrera et al, 2000). Thus the LPS model has served as a valuable tool in deciphering the role of glial cells, especially microglia, in the DA neurodegeneration process and has been described by many as the neuroinflammatory model of PD.…”