Inflammation and fatigue in early, untreated Parkinson's Disease

Objectives: Parkinson's disease (PD)-related fatigue is a significant clinical problem, and the pathological processes that cause fatigue remain unknown. The aim of the present study was to explore the possible association of peripheral inflammation markers and fatigue in PD. Materials & methods: We included 47 drug naïve, newly diagnosed PD patients with low (≤3.0) or high (>5.5) fatigue levels as evaluated by the Fatigue Severity Scale (FSS). Strict diagnostic criteria were applied for inclusion. Patients with possible confounding causes for fatigue were excluded. Serum concentrations of a panel of inflammatory markers (IL-8, TNF-α, MCP1, MIP-1β, IL-6, IL-6R, p-selectin, E-selectin-1, ICAM, VCAM-1, CCL5, IL1-Ra, and TNFR1) were measured using ELISA technology in PD patients with and without fatigue to assess the potential relationships of fatigue in newly diagnosed, treatment-naïve patients. Results: Fatigued PD patients had significantly higher levels of the IL-1 receptor antagonist (IL1-Ra) (1790 pg/mL (SD1007) vs 1262 pg/mL (SD379)) and of the adhesion molecule VCAM 1 (1071 ng/mL (SD276) vs 895 ng/mL (SD229)) than non-fatigued patients. A binary logistic regression model, including high or low FSS score as the dependent variable and UPDRS motor score, MADRS, MMSE, ESS, and IL1-Ra/VCAM-1 as independent variables, showed a significant effect both for IL1-Ra and VCAM-1. Conclusions: Higher serum levels of the inflammatory molecules IL1-Ra and VCAM-1 were associated with higher fatigue levels in patients with newly diagnosed, drug-naïve PD. These findings highlight an altered immune response as a potential contributor to PD-related fatigue, from the earliest clinical stages of the disease.