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Original Investigation
November 2016

Aberrations in Peripheral Inflammatory Cytokine Levels in Parkinson DiseaseA Systematic Review and Meta-analysis

Author Affiliations
  • 1Center on Translational Neuroscience, College of Life and Environmental Sciences, MinZu University of China, Beijing, China
  • 2Section on Cellular Neurobiology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
JAMA Neurol. 2016;73(11):1316-1324. doi:10.1001/jamaneurol.2016.2742
Key Points

Question  Are peripheral blood levels of inflammatory cytokines altered in patients with Parkinson disease (PD)?

Findings  In this meta-analysis of 25 studies with 2654 unique participants, patients with PD demonstrated significantly higher blood levels of interleukin 6 (IL-6), tumor necrosis factor, IL-1β, IL-2, IL-10, C-reactive protein, and RANTES (regulated on activation, normal T-expressed, and presumably secreted) compared with healthy control individuals.

Meaning  This study provides a novel perspective into the etiology of PD, and future investigations into the cytokines as biomarkers and therapeutic targets for PD may be warranted.


Importance  The 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 Relevance  The 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.