Aberrations in Peripheral Inflammatory Cytokine Levels in Parkinson Disease: A Systematic Review and Meta-analysis.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational case-control studies.
PubMed 27668667 · doi:10.1001/jamaneurol.2016.2742
What was done
A systematic review and meta-analysis searched PubMed, PsycINFO, and the Cochrane Library through March 2016 for English-language studies evaluating peripheral blood cytokine levels in patients with Parkinson disease (PD) compared to healthy controls. Studies were excluded if they analyzed in vitro stimulated/unstimulated levels, contained overlapping samples, assessed cytokines in fewer than 3 studies, or evaluated patients not diagnosed with PD at blood sampling. Data from 25 studies (1,547 PD patients, 1,107 healthy controls) were pooled using a random-effects model, and effect sizes were converted to Hedges g.
What was found
Compared with healthy controls, patients with PD had significantly elevated peripheral blood concentrations of: - Interleukin 6 (IL-6): Hedges g = 0.325 (95% CI, 0.007 to 0.643; P = .045; 13 studies) - Tumor necrosis factor (TNF): Hedges g = 0.354 (95% CI, 0.144 to 0.563; P = .001; 9 studies) - IL-1β: Hedges g = 0.382 (95% CI, 0.142 to 0.621; P = .002; 6 studies) - C-reactive protein (CRP): Hedges g = 0.323 (95% CI, 0.052 to 0.593; P = .02; 6 studies) - IL-10: Hedges g = 0.329 (95% CI, 0.051 to 0.607; P = .02; 5 studies) - RANTES: Hedges g = 0.605 (95% CI, 0.111 to 1.099; P = .02; 5 studies) - IL-2: Hedges g = 0.789 (95% CI, 0.105 to 1.472; P = .02; 3 studies) No significant differences were identified for interferon-γ (Hedges g = 0.745; 95% CI, -0.192 to 1.682; P = .12; 5 studies), IL-4 (Hedges g = 0.031; 95% CI, -0.191 to 0.253; P = .79; 3 studies), or IL-8 (Hedges g = 0.072; 95% CI, -0.136 to 0.279; P = .50; 3 studies).
Why it matters
This study provides pooled clinical evidence that Parkinson disease is characterized by a systemic peripheral inflammatory response involving multiple pro-inflammatory and immunoregulatory cytokines.
Limits
The included studies were observational case-control comparisons, preventing determination of whether peripheral cytokine changes are causative drivers or secondary markers of PD pathology. Several cytokines (e.g., IL-2, IL-4, IL-8) were evaluated in only 3 studies, yielding wide confidence intervals. Search criteria were restricted to English-language publications, and the abstract provides no data on potential confounding by PD medications, disease duration, or medical comorbidities.
Cited by
- supports Patients with Parkinson's disease show elevated levels of pro-inflammatory cytokines such as TNF-alpha and IL-6.