Peripheral inflammatory cytokines and motor symptoms in persons with Parkinson's disease

Abstract

Background: Many of the motor symptoms of Parkinson's disease (PD) impact quality of life and are not fully ameliorated by current pharmacological and surgical treatments. A better understanding of the pathophysiology underlying these symptoms is needed. Previous research has suggested that inflammation may play a significant role in PD pathophysiology and progression, but there is limited research exploring how inflammation directly relates to motor symptoms in PD. Thus, the purpose of this study was to evaluate associations between peripheral immune inflammatory markers and motor symptoms of PD, specifically, tremor, bradykinesia, and postural and gait instability. We hypothesized that peripheral inflammatory cytokines would predict the severity of motor symptoms in persons with PD, and that there will be higher levels of peripheral inflammatory cytokine markers in persons with PD when compared to age-matched healthy older adults.

Methods: Twenty-six participants with PD and fourteen healthy older adults completed the study. For participants with PD, the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS) was recorded and scored by two Movement Disorders Neurologists masked to the study. A blood sample was collected from both participants with PD and the healthy older adults. Through the MILLIPLEX® map High Sensitivity Human Cytokine Kit, key inflammation-related markers were analyzed (TNF-α, IFN-γ, IL-1β, IL-8, IL-2, IL-7, IL-5, IL-13, IL, 4, IL-10 IL-12p70, GM-CSF, and IL-6).

Results: Results revealed significantly higher levels of IL-6 in persons with PD when compared to healthy older adults (p ​= ​0.005). Moreover, results revealed that higher levels of IL-4 (p ​= ​0.011) and lower levels of IFNγ (p ​= ​0.003) significantly predicted more severe tremor in persons with PD. No other associations between the peripheral inflammation markers and other motor symptoms were observed.

Conclusions: Overall, these results are consistent with a growing body of literature that implicates inflammatory cytokines in the PD, and further suggests that inflammatory cytokines, or lack thereof, may be associated with tremor in persons with PD.

Keywords: BDI, Beck Depression Inventory; IFNγ, Interferon gamma; IL, interleukins; Inflammatory cytokines; MDS-UPDRS, Movement Disorders Society Unified Parkinson's Disease Rating Scale; MMSE, Mini-Mental State Exam; Motor impairments; Movement Disorders Society Unified Parkinson's Disease Rating Scale; PD, Parkinson's disease; Parkinson's disease; Peripheral inflammation; TNFα, Tumor necrosis factor-alpha; Th cells, T helper cells.

Fig. 1

Levels inflammatory markers in patients with Parkinson's disease (black bars) and controls (gray bars). Bars represent mean values, and T-bars indicate standard errors; ∗P ​< ​0.05.

Fig. 2

Peripheral inflammatory cytokines in persons with PD and healthy older adults. a) and b) inflammation-related cytokines, c) mixed-function cytokines, and d) T helper type 2 (Th2) related cytokines. Data were obtained from the blood of persons with PD and healthy older adults.