Insights into Neuroinflammation in Parkinson’s Disease: From Biomarkers to Anti-Inflammatory Based Therapies

Table 1

Evidence regarding the contribution of immune dysfunction and/or inflammation in Parkinson’s disease.

Evidence	Source	Results	Reference
CNS inflammation	Human brain	Significant increase in the number of reactive microglia in the substantia nigra of PD patients.	[9, 12]
		Coexistence of α-synuclein and activated microglia.	[15]
		Higher expression/increased levels of inflammatory mediators in PD brains.	[13, 16–18]
	Human CSF samples	Increased levels of IL-1β, IL-2, IL-4, IL-6, TGF-α, free TGF-β1, and total TGF-β2 in the CSF of PD patients.	[30–32]
Peripheral inflammation	Serum/plasma samples	Increased levels of IFN-γ, IL-1β, IL-2, IL-3, IL-10, MIF, TNF-α, and its soluble receptors sTNFR1 and sTNFR2 in PD patients samples.	[48–58]
	Supernatants from cell cultures	MCP-1, MIP-1α, IL-8, IFN-γ, IL-1β, and TNF-α levels were significantly higher in PD patients.	[65]
	Blood leukocytes	PD patients exhibited lower total lymphocyte counts; decrease in the percentage of T (CD3+) and B (CD19+) cells and reduction in T helper (Th, CD4+) lymphocytes; higher percentage of NK cells.	[52, 61, 71–74, 77]
Genetic evidence	DNA extracted from brain, blood, or buccal samples	Enhancement in IL-1β 511, IL-6, and TNF-α polymorphisms.	[21–24]
Epidemiological evidence	Clinical and population-based studies	NSAIDs use was associated with a lower risk for PD.	[91, 92, 94, 95, 104].
		IFN-α-induced Parkinsonism in chronic hepatitis [67–69].	[67–69]
		The relationship between PD and systemic infections (severe influenza).	[70]

CSF: cerebrospinal fluid; CNS: central nervous system; IFN: interferon, IL: interleukin; MIF: migration inhibitory factor; MCP: monocyte chemotactic protein; MIP: macrophage inflammatory protein; NSAIDs: nonsteroidal anti-inflammatory drugs; PD: Parkinson’s disease; TGF: transforming growth factor; TNF: tumor necrosis factor; sTNFR: TNF soluble receptor.