Aberrations in Peripheral Inflammatory Cytokine Levels in Parkinson Disease

Abstract

IMPORTANCEThe association of nonmotor features and Parkinson disease (PD) is increasingly recognized. Evidence suggests that inflammation may play a role in PD pathologic features and symptoms.OBJECTIVE To quantitatively summarize the peripheral inflammatory cytokine data available for patients with PD.DATA SOURCE A systematic search of peer-reviewed English-language articles from PubMed, PsycINFO, and the Cochrane Library without year limitation was performed from December 7, 2015, to March 23, 2016. The search terms included inflammation or cytokine or chemokine or tumor necrosis factor or interleukin or interferon or C-reactive protein AND Parkinson disease.STUDY SELECTION Studies were included if they provided data on peripheral blood cytokine concentrations in patients with PD and a healthy control group. Studies were excluded if they contained in vitro analysis of stimulated or unstimulated levels of cytokines, samples that overlapped with other studies, patients not diagnosed with PD at blood sampling, or if the cytokine analyzed was assessed in fewer than 3 studies.DATA EXTRACTION AND SYNTHESIS Data were extracted from the 25 included studies encompassing 1547 unique patients with PD and 1107 unique controls by 2 independent investigators. Data were pooled using a random-effects model with the Comprehensive Meta-analysis software. Effect sizes were generated as standardized mean differences of cytokine concentrations between patients with PD and healthy controls and converted to the Hedges g statistic.MAIN OUTCOMES AND MEASURES Blood cytokine concentrations in patients with PD compared with controls. Aberrations in peripheral cytokine levels were hypothesized to be related to PD. RESULTS Among the 2654 study participants, concentrations of interleukin 6 (IL-6) (Hedges g, 0.325; 95% CI, 0.007-0.643; P = .045) in 13 studies, tumor necrosis factor (Hedges g, 0.354; 95% CI, 0.144-0.563; P = .001) in 9 studies, IL-1β (Hedges g, 0.382; 95% CI, 0.142-0.621; P = .002) in 6 studies, C-reactive protein (Hedges g, 0.323; 95% CI, 0.052-0.593; P = .02) in 6 studies, IL-10 (Hedges g, 0.329; 95% CI, 0.051-0.607; P = .02) in 5 studies, RANTES (regulated on activation, normal T-expressed, and presumably secreted) (Hedges g, 0.605; 95% CI, 0.111-1.099; P = .02) in 5 studies, and IL-2 (Hedges g, 0.789; 95% CI, 0.105-1.472; P = .02) in 3 studies were significantly higher in patients with PD compared with healthy controls. No differences were found between patients with PD and healthy controls for concentrations of interferon-γ (Hedges g, 0.745; 95% CI, −0.192 to 1.682; P = .12) in 5 studies, IL-4 (Hedges g, 0.031; 95% CI, −0.191 to 0.253; P = .79) in 3 studies, and IL-8 (Hedges g, 0.072; 95% CI, −0.136 to 0.279; P = .50) in 3 studies. CONCLUSIONS AND RELEVANCEThe findings of the meta-analysis demonstrated higher peripheral concentrations of IL-6, tumor necrosis factor, IL-1β, IL-2, IL-10, C-reactive protein, and RANTES in patients with PD, strengthening the clinical evidence that PD is accompanied by an inflammatory response.

Modulation of Microglial Activity by Rho-Kinase (ROCK) Inhibition as Therapeutic Strategy in Parkinson’s Disease and Amyotrophic Lateral Sclerosis

“…Different PET studies could confirm an increased microglial activation in the midbrain of PD patients that was correlated to disease progression (Ouchi et al, 2005; Gerhard et al, 2006; Koshimori et al, 2015). This goes in line with a study reporting that the pro-inflammatory cytokines TNFα, IL-6 and IL-1β were elevated in the cerebrospinal fluid (CSF) of PD patients (Qin et al, 2016). So far, all evidence on hand points towards an increased microglial activation with a pro-inflammatory “M1” phenotype that might contribute to PD progression.…”

A Case-Control Association Study ofRANTES (-28C>G)Polymorphism as a Risk Factor for Parkinson’s Disease in Isparta, Turkey

“…Studies reporting increased serum RANTES levels in association with IL-15, IL-8, and MCP-1 in PD patients suggest that the dysregulation in the peripheral cytokine network might be related to the pathogenesis and underlying neurodegeneration [19, 27, 28]. In addition, RANTES serum levels were reported to correlate with disease severity [29, 30]. …”

Serum Lymphocyte-Associated Cytokine Concentrations Change More Rapidly over Time in Multiple System Atrophy Compared to Parkinson Disease

“…Patients with MSA were found to have an increase in proinflammatory TNFα in serum [6]. Other evidence shows increased peripheral inflammatory cytokines, including IL-6, TNFα, and IL-1β in the serum of patients with PD [7]. Epidemiologic evidence also indicated that increased serum levels of IL-6 were associated with a greater risk of PD development [8], though the results of subsequent studies were variable regarding significant increases or associations of IL-6 with symptoms [9–12].…”